Epithelial Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer
Conditions
Keywords
Epithelial ovarian cancer, Fallopian tube cancer, Primary peritoneal cancer, IMGN853, ADC, Antibody drug conjugate, ImmunoGen, Antibody, Phase 1, Folate receptor alpha, Mirvetuximab
Brief summary
This study comprises a Dose Escalation phase followed by a Dose Expansion phase. Dose Escalation part of the study will assess the safety and tolerability and determine the maximum tolerated dose (MTD) as the recommended Phase 2 (RP2D) dose for each regimen. Participants will be assigned to one of the 4 regimens in Dose Escalation phase: Regimen A: mirvetuximab soravtansine administered with bevacizumab; Regimen B: mirvetuximab soravtansine administered with carboplatin; Regimen C: mirvetuximab soravtansine administered with pegylated liposomal doxorubicin; or Regimen D: mirvetuximab soravtansine administered with pembrolizumab. Dose Expansion of the study will further assess safety, tolerability and preliminary anti-tumor activity of mirvetuximab soravtansine. A Dose Expansion phase is planned for Regimen A and Regimen D and will open pending Sponsor decision; participants enrolled in the Dose Expansion phase will receive study treatment at the MTD or RP2D determined during Dose Escalation. For Regimen A, participants in the Dose Expansion phase may be enrolled according to prior exposure to bevacizumab into 3 Dose Expansion Cohorts as follows: 1) Dose Expansion Cohort 1: bevacizumab naïve; 2) Dose Expansion Cohort 2: bevacizumab pretreated; and 3) Dose Expansion Cohort 3: one to three prior treatments, one of which could have been bevacizumab. A triplet Regimen (Regimen E: mirvetuximab soravtansine + bevacizumab + carboplatin) will be opened to evaluate the safety and tolerability and to assess any early signs of activity in participants dosed with the combination regimen. All mirvetuximab soravtansine doses were calculated according to adjusted ideal body weight.
Detailed description
Participants will continue to receive mirvetuximab soravtansine and/or the combination agent until progressive disease (PD), unacceptable toxicity, or withdrawal of consent, whichever comes first, or until the Sponsor terminates the study.
Interventions
DRUGMirvetuximab soravtansine
DRUGBevacizumab
DRUGCarboplatin
DRUGPegylated Liposomal Doxorubicin
DRUGPembrolizumab
Sponsors
ImmunoGen, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with advanced epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer * Folate receptor α (FRα) positive tumor expression as defined in the protocol * Willing to provide an archival tumor tissue block or slides or undergo tumor biopsy. New tumor biopsy (Cycle 2 Day 8) is required for Regimen D. * Measurable disease
Exclusion criteria
* Primary platinum-refractory disease * Diagnosis of clear cell, low grade ovarian cancer or mixed tumors * Serious concurrent illness or clinically relevant active infection, including but not limited to known diagnosis of human immunodeficiency virus (HIV) and hepatitis B or C, as defined in the protocol * Active autoimmune disease requiring systemic therapy in past 2 years (for Regimen D only) * Women who are pregnant or breastfeeding * Male participants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 238.3 weeks) | Adverse events (AEs) were any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function that developed or worsened during the clinical study, not necessarily having a causal relationship to study drug. Severity was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death. Serious AEs included death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes previously listed. TEAEs were any AE that emerged on or after the first dose, and within 30 days of the last dose. Serious and other non-serious AEs regardless of causality are reported in the AE module. |
| Dose Expansion (Regimens A and D) and Triplet (Regimen E): Objective Response Rate (ORR); Percentage of Participants With Confirmed Response, as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | From first dose of study drug until first CR or PR (maximum exposure: 238.3 weeks) | ORR was defined as percentage of participants with confirmed response (complete response \[CR\] + partial response \[PR\]). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR: At least 30 percent (%) decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD. The 95% confidence interval (CI) was based on binomial distribution. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | From first dose of study drug until the date of PD or death by any cause (maximum exposure: 238.3 weeks) | PFS was defined as the time from the date of the first dose of study drug until the date of PD or death from any cause, whichever occurred first, estimated using the Kaplan-Meier method. PFS was defined based on radiological assessments and determined by the investigator. PD was defined as at least a 20% increase in the SLD of target lesions, taking as reference the smallest (nadir) SLD since and including baseline. In addition to the relative increase of 20%, the SLD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. |
| Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | From the date of first objective response to the time of PD (maximum exposure: 238.3 weeks) | DOR was defined as the time from the date of the first response (CR or PR), to the date of PD or death from any cause, whichever occurred first. DOR was only defined for patients who had a best overall response of CR or PR, estimated using the Kaplan-Meier method. The response-evaluable population included all patients with radiographic assessment at baseline, who received at least 1 dose of combination treatment and had at least 1 post-dose radiographic tumor assessment or who died within 105 days of first dose. |
| Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | From first dose of study drug until first CR or PR (maximum exposure: 238.3 weeks) | A CA-125 response was defined as a ≥ 50% reduction in CA-125 levels from baseline. GCIG CA125 response rate was defined as the number of participants with a CA-125 confirmed response divided by the number of participants in the CA-125 response-evaluable population multiplied by 100. The CA-125 evaluable population included all participants whose pretreatment sample was ≥2.0 times the upper limit of normal, within 2 weeks prior to the first dose of combination treatment, and who had at least 1 post-baseline CA-125 evaluation. |
| Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of end of infusion [EOI], and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C) | Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. Results are reported in micrograms/milliliter (µg/mL). |
| PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of end of infusion [EOI], and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C) | Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. Results are reported in nanograms (ng)/mL. |
| PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C) | Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. Results are reported in mg\*hours (h)/mL. |
| PK Parameter: AUCinf of Intact DM4 and SmDM4 | Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C) | Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. Note that '9999' is used because AUCinf cannot be calculated for n\<3. |
| Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1 | From first dose of study drug until first CR or PR (maximum exposure: 238.3 weeks) | ORR was defined as percentage of participants with confirmed response (CR + PR). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least 30% decrease in the SLD of target lesions, taking as reference the baseline SLD. |
| PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C) | Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. |
| PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C) | Blood samples from participants were analyzed to characterize PK when administered in 3- or 4-week cycles. |
| PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (up to 336 hours) (additionally at Day 22 for Regimen C) | Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. PK parameters were derived using non-compartmental PK analysis. |
| Plasma Concentration of Bevacizumab | At end of infusion (EOI) of Cycle 1; and at pre-infusion and EOI of Cycles 2 to 6 | Blood samples from participants at the end of infusion were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. |
| Plasma Concentration of Carboplatin | At end of infusion, 6 and 24 hours post-infusion of Cycle 1; and at pre-infusion and end of infusion of Cycles 2, 4, 5 and 6; at pre-infusion, end of infusion and 6 and 24 hours post-infusion of Cycle 3 | Blood samples from participants at the end of infusion were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. |
| Plasma Concentration of Pegylated Liposomal Doxorubicin | At end of infusion of Cycle 1; and at pre-infusion and end of infusion of Cycles 2 to 6 | Blood samples from participants at the end of infusion were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. |
| Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) Response to Mirvetuximab Soravtansine | From first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 283.3 weeks) | Blood samples were collected to measure the presence of ADAs for mirvetuximab soravtansine. Seronegative is defined as a participant that tests negative at all visits. Treatment-emergent ADA is defined as a participant that is seronegative prior to dosing on Day 1 of Cycle 1 and tests positive in both screening and confirmatory assays at one or more subsequent visits. Treatment-unaffected ADA is defined as a participant test positive in both screening and confirmatory assays prior to dosing on Day 1 of Cycle 1 with a post-dose titer increase of less than or equal to 4-fold (based on a 2-fold sample dilution). Treatment-boosted ADA is defined as a participant test positive in both screening and confirmatory assays prior to dosing on Day 1 of Cycle 1 with a post-dose titer increase of more than a 4-fold increase (based on a 2-fold sample dilution). |
| PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (up to 336 hours) (additionally at Day 22 for Regimen C) | Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. PK parameters were calculated using standard non-compartmental methods. The terminal t½ is an estimate (extrapolation) of the time it takes for the concentration or amount in the body of that drug to be reduced by exactly one-half (50%). If extrapolated AUC was greater than 20% (due to insufficient number of participants with data samples) the upper range of t½ was not reported. |
| PK Parameter: CL of DM4 and SmDM4 | Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C) | Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. |
Countries
Belgium, Canada, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Regimen A Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg Participants were administered mirvetuximab soravtansine 5 mg/kg + bevacizumab 15 mg/kg on Day 1 of each 21-day cycle. | 3 |
| Regimen A Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg Participants were administered mirvetuximab soravtansine 6 mg/kg + bevacizumab 15 mg/kg on Day 1 of each 21-day cycle. | 11 |
| Regimen A Dose Expansion Cohort 1: Bevacizumab-naïve Participants not previously treated with bevacizumab (bevacizumab naïve) were administered mirvetuximab soravtansine 6 mg/kg + bevacizumab 15 mg/kg on Day 1 of each 21-day cycle. | 21 |
| Regimen A Dose Expansion Cohort 2: Bevacizumab Pre-treated Participants who were pre-treated with bevacizumab were administered mirvetuximab soravtansine 6 mg/kg + bevacizumab 15 mg/kg on Day 1 of each 21-day cycle. | 34 |
| Regimen A Dose Expansion Cohort 3: Pt-agnostic: Participants with at least 1 but no more than 3 prior systemic treatment regimens, where prior regimens may have included bevacizumab were administered mirvetuximab soravtansine 6 mg/kg + bevacizumab 15 mg/kg. | 60 |
| Regimen B Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 Participants were administered mirvetuximab soravtansine 5 mg/kg + carboplatin AUC4 on Day 1 of each 21-day cycle. | 4 |
| Regimen B Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 Participants were administered mirvetuximab soravtansine 5 mg/kg + carboplatin AUC5 on Day 1 of each 21-day cycle. | 4 |
| Regimen B Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 Participants were administered mirvetuximab soravtansine 6 mg/kg + carboplatin AUC5 on Day 1 of each 21-day cycle. | 10 |
| Regimen C Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 Participants were administered mirvetuximab soravtansine 5 mg/kg + PLD 30 mg/m\^2 on Day 1 of each 28-day cycle. | 4 |
| Regimen C Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 Participants were administered mirvetuximab soravtansine 5 mg/kg + PLD 40 mg/m\^2 on Day 1 of each 28-day cycle. | 5 |
| Regimen C Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 Participants were administered mirvetuximab soravtansine 6 mg/kg + PLD 40 mg/m\^2 on Day 1 of each 28-day cycle. | 7 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg Participants were administered mirvetuximab soravtansine 5 mg/kg + pembrolizumab 200 mg on Day 1 of each 21-day cycle. | 4 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg Participants were administered mirvetuximab soravtansine 6 mg/kg + pembrolizumab 200 mg on Day 1 of each 21-day cycle. | 10 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg Participants were administered mirvetuximab soravtansine 6 mg/kg + pembrolizumab 200 mg on Day 1 of each 21-day cycle. | 46 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin Participants were administered mirvetuximab soravtansine 6 mg/kg + bevacizumab 15 mg/kg + carboplatin AUC5 on Day 1 of each 21-day cycle. | 41 |
| Total | 264 |
Baseline characteristics
| Characteristic | Regimen A Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Regimen A Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Regimen A Dose Expansion Cohort 1: Bevacizumab-naïve | Regimen A Dose Expansion Cohort 2: Bevacizumab Pre-treated | Regimen A Dose Expansion Cohort 3: Pt-agnostic: | Regimen B Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Regimen B Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Regimen B Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Regimen C Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Regimen C Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | Regimen C Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.3 years STANDARD_DEVIATION 11.85 | 65.5 years STANDARD_DEVIATION 8.43 | 62.2 years STANDARD_DEVIATION 7.4 | 61.4 years STANDARD_DEVIATION 9.99 | 61.4 years STANDARD_DEVIATION 9.87 | 59.3 years STANDARD_DEVIATION 9.14 | 67.0 years STANDARD_DEVIATION 7.07 | 66.0 years STANDARD_DEVIATION 10.33 | 59.5 years STANDARD_DEVIATION 12.07 | 65.2 years STANDARD_DEVIATION 4.66 | 60.6 years STANDARD_DEVIATION 5.35 | 58.3 years STANDARD_DEVIATION 6.18 | 63.5 years STANDARD_DEVIATION 10.81 | 61.1 years STANDARD_DEVIATION 8.64 | 63.8 years STANDARD_DEVIATION 9.4 | 62.3 years STANDARD_DEVIATION 9.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 11 Participants | 21 Participants | 32 Participants | 58 Participants | 4 Participants | 4 Participants | 9 Participants | 4 Participants | 4 Participants | 7 Participants | 4 Participants | 10 Participants | 45 Participants | 39 Participants | 255 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 3 Participants | 10 Participants | 21 Participants | 32 Participants | 53 Participants | 4 Participants | 4 Participants | 10 Participants | 4 Participants | 5 Participants | 7 Participants | 4 Participants | 10 Participants | 43 Participants | 39 Participants | 249 Participants |
| Sex: Female, Male Female | 3 Participants | 11 Participants | 21 Participants | 34 Participants | 60 Participants | 4 Participants | 4 Participants | 10 Participants | 4 Participants | 5 Participants | 7 Participants | 4 Participants | 10 Participants | 46 Participants | 41 Participants | 264 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 5 / 126 | 0 / 4 | 0 / 4 | 0 / 10 | 0 / 4 | 0 / 5 | 0 / 7 | 0 / 4 | 4 / 56 | 2 / 41 |
| other Total, other adverse events | 3 / 3 | 125 / 126 | 4 / 4 | 4 / 4 | 10 / 10 | 4 / 4 | 4 / 5 | 7 / 7 | 4 / 4 | 56 / 56 | 41 / 41 |
| serious Total, serious adverse events | 2 / 3 | 49 / 126 | 2 / 4 | 4 / 4 | 3 / 10 | 1 / 4 | 2 / 5 | 3 / 7 | 2 / 4 | 25 / 56 | 17 / 41 |
Outcome results
Primary
Dose Expansion (Regimens A and D) and Triplet (Regimen E): Objective Response Rate (ORR); Percentage of Participants With Confirmed Response, as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
ORR was defined as percentage of participants with confirmed response (complete response \[CR\] + partial response \[PR\]). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR: At least 30 percent (%) decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD. The 95% confidence interval (CI) was based on binomial distribution.
Time frame: From first dose of study drug until first CR or PR (maximum exposure: 238.3 weeks)
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Dose Expansion (Regimens A and D) and Triplet (Regimen E): Objective Response Rate (ORR); Percentage of Participants With Confirmed Response, as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 52 percentage of participants |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Dose Expansion (Regimens A and D) and Triplet (Regimen E): Objective Response Rate (ORR); Percentage of Participants With Confirmed Response, as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 29 percentage of participants |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Dose Expansion (Regimens A and D) and Triplet (Regimen E): Objective Response Rate (ORR); Percentage of Participants With Confirmed Response, as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 50 percentage of participants |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Dose Expansion (Regimens A and D) and Triplet (Regimen E): Objective Response Rate (ORR); Percentage of Participants With Confirmed Response, as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 27 percentage of participants |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Dose Expansion (Regimens A and D) and Triplet (Regimen E): Objective Response Rate (ORR); Percentage of Participants With Confirmed Response, as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 83 percentage of participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Adverse events (AEs) were any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function that developed or worsened during the clinical study, not necessarily having a causal relationship to study drug. Severity was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death. Serious AEs included death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes previously listed. TEAEs were any AE that emerged on or after the first dose, and within 30 days of the last dose. Serious and other non-serious AEs regardless of causality are reported in the AE module.
Time frame: From first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 238.3 weeks)
Population: All participants who were enrolled and received at least 1 dose of study drug. Data were reported by dose group and where applicable the dose-escalation and expansion phases were combined to report data by dose group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade >=3 TEAEs | 2 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 2 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 3 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 49 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 126 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade >=3 TEAEs | 85 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 4 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade >=3 TEAEs | 2 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 2 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade >=3 TEAEs | 4 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 4 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 4 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade >=3 TEAEs | 7 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 3 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 10 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 1 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 4 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade >=3 TEAEs | 2 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade >=3 TEAEs | 3 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 4 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 2 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade >=3 TEAEs | 6 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 7 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 3 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade >=3 TEAEs | 1 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 4 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 2 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade >=3 TEAEs | 30 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 25 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 56 Participants |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAE | 41 Participants |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 17 Participants |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade >=3 TEAEs | 37 Participants |
Secondary
Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1
ORR was defined as percentage of participants with confirmed response (CR + PR). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least 30% decrease in the SLD of target lesions, taking as reference the baseline SLD.
Time frame: From first dose of study drug until first CR or PR (maximum exposure: 238.3 weeks)
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1 | 0 percentage of participants |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1 | 45 percentage of participants |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1 | 50 percentage of participants |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1 | 50 percentage of participants |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1 | 89 percentage of participants |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1 | 0 percentage of participants |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1 | 20 percentage of participants |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1 | 29 percentage of participants |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1 | 25 percentage of participants |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1 | 50 percentage of participants |
Secondary
Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment
DOR was defined as the time from the date of the first response (CR or PR), to the date of PD or death from any cause, whichever occurred first. DOR was only defined for patients who had a best overall response of CR or PR, estimated using the Kaplan-Meier method. The response-evaluable population included all patients with radiographic assessment at baseline, who received at least 1 dose of combination treatment and had at least 1 post-dose radiographic tumor assessment or who died within 105 days of first dose.
Time frame: From the date of first objective response to the time of PD (maximum exposure: 238.3 weeks)
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose. Only participants who had best overall response of CR or PR were analyzable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | NA months |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | 11.96 months |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | 14.06 months |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | 10.38 months |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | NA months |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | 31.77 months |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | 12.12 months |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | NA months |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | NA months |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | 3.42 months |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | 8.31 months |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | 4.37 months |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment | 10.87 months |
Secondary
Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment
A CA-125 response was defined as a ≥ 50% reduction in CA-125 levels from baseline. GCIG CA125 response rate was defined as the number of participants with a CA-125 confirmed response divided by the number of participants in the CA-125 response-evaluable population multiplied by 100. The CA-125 evaluable population included all participants whose pretreatment sample was ≥2.0 times the upper limit of normal, within 2 weeks prior to the first dose of combination treatment, and who had at least 1 post-baseline CA-125 evaluation.
Time frame: From first dose of study drug until first CR or PR (maximum exposure: 238.3 weeks)
Population: CA125 Evaluable Population: All participants whose pretreatment sample is ≥ 2.0 times the upper limit of normal (ULN), within 2 weeks prior to the first dose of combination treatment, and who have at least 1 post-baseline CA125 evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 100 percentage of participants |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 60 percentage of participants |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 75 percentage of participants |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 65 percentage of participants |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 71 percentage of participants |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 67 percentage of participants |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 100 percentage of participants |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 86 percentage of participants |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 0 percentage of participants |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 50 percentage of participants |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 50 percentage of participants |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 0 percentage of participants |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 63 percentage of participants |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 46 percentage of participants |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment | 100 percentage of participants |
Secondary
Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) Response to Mirvetuximab Soravtansine
Blood samples were collected to measure the presence of ADAs for mirvetuximab soravtansine. Seronegative is defined as a participant that tests negative at all visits. Treatment-emergent ADA is defined as a participant that is seronegative prior to dosing on Day 1 of Cycle 1 and tests positive in both screening and confirmatory assays at one or more subsequent visits. Treatment-unaffected ADA is defined as a participant test positive in both screening and confirmatory assays prior to dosing on Day 1 of Cycle 1 with a post-dose titer increase of less than or equal to 4-fold (based on a 2-fold sample dilution). Treatment-boosted ADA is defined as a participant test positive in both screening and confirmatory assays prior to dosing on Day 1 of Cycle 1 with a post-dose titer increase of more than a 4-fold increase (based on a 2-fold sample dilution).
Time frame: From first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 283.3 weeks)
Population: The immunogenicity population included all participants who received at least 1 dose of study drug and have evaluable immunogenicity data. As per analysis plan, all regimens (arms/groups) were combined for each phase of the study (dose escalation and dose expansion) for analysis of ADA.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) Response to Mirvetuximab Soravtansine | Treatment-unaffected ADA | 7 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) Response to Mirvetuximab Soravtansine | Seronegative | 51 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) Response to Mirvetuximab Soravtansine | Treatment-emergent ADA | 3 Participants |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) Response to Mirvetuximab Soravtansine | Treatment-boosted ADA | 1 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) Response to Mirvetuximab Soravtansine | Treatment-emergent ADA | 11 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) Response to Mirvetuximab Soravtansine | Treatment-unaffected ADA | 11 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) Response to Mirvetuximab Soravtansine | Treatment-boosted ADA | 5 Participants |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) Response to Mirvetuximab Soravtansine | Seronegative | 175 Participants |
Secondary
Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody
Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. Results are reported in micrograms/milliliter (µg/mL).
Time frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of end of infusion [EOI], and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose. The 'Number Analyzed' signifies participants evaluable for the specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 135 µg/mL | Geometric Coefficient of Variation 9.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | NA µg/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 121 µg/mL | Geometric Coefficient of Variation 11.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | NA µg/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 147 µg/mL | Geometric Coefficient of Variation 25.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 122 µg/mL | Geometric Coefficient of Variation 12.9 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 148 µg/mL | Geometric Coefficient of Variation 15.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 137 µg/mL | Geometric Coefficient of Variation 14.5 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 152 µg/mL | Geometric Coefficient of Variation 31.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 159 µg/mL | Geometric Coefficient of Variation 30.4 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 177 µg/mL | Geometric Coefficient of Variation 26.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 164 µg/mL | Geometric Coefficient of Variation 12.4 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 175 µg/mL | Geometric Coefficient of Variation 22.7 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 148 µg/mL | Geometric Coefficient of Variation 24.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 174 µg/mL | Geometric Coefficient of Variation 14.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 159 µg/mL | Geometric Coefficient of Variation 17.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 150 µg/mL | Geometric Coefficient of Variation 17.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 153 µg/mL | Geometric Coefficient of Variation 13 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 137 µg/mL | Geometric Coefficient of Variation 144 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 180 µg/mL | Geometric Coefficient of Variation 41 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 118 µg/mL | Geometric Coefficient of Variation 18.2 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 46 µg/mL | Geometric Coefficient of Variation 999 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 118 µg/mL | Geometric Coefficient of Variation 15.4 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 57.9 µg/mL | Geometric Coefficient of Variation 238 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 121 µg/mL | Geometric Coefficient of Variation 15.1 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 108 µg/mL | Geometric Coefficient of Variation 15.7 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 122 µg/mL | Geometric Coefficient of Variation 20.9 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 102 µg/mL | Geometric Coefficient of Variation 16.4 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 149 µg/mL | Geometric Coefficient of Variation 15.5 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 144 µg/mL | Geometric Coefficient of Variation 19.3 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 129 µg/mL | Geometric Coefficient of Variation 11.8 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 147 µg/mL | Geometric Coefficient of Variation 12.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | NA µg/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 111 µg/mL | Geometric Coefficient of Variation 23.5 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | NA µg/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 115 µg/mL | Geometric Coefficient of Variation 21.5 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 114 µg/mL | Geometric Coefficient of Variation 15.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 137 µg/mL | Geometric Coefficient of Variation 15.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 124 µg/mL | Geometric Coefficient of Variation 3.32 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 114 µg/mL | Geometric Coefficient of Variation 18.6 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 152 µg/mL | Geometric Coefficient of Variation 17.2 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 146 µg/mL | Geometric Coefficient of Variation 16.8 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 140 µg/mL | Geometric Coefficient of Variation 19 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 142 µg/mL | Geometric Coefficient of Variation 6.03 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 94.7 µg/mL | Geometric Coefficient of Variation 34.2 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 114 µg/mL | Geometric Coefficient of Variation 20 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 112 µg/mL | Geometric Coefficient of Variation 4 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 114 µg/mL | Geometric Coefficient of Variation 17.8 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 124 µg/mL | Geometric Coefficient of Variation 11.8 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 165 µg/mL | Geometric Coefficient of Variation 10.6 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 160 µg/mL | Geometric Coefficient of Variation 23 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 156 µg/mL | Geometric Coefficient of Variation 13.2 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 146 µg/mL | Geometric Coefficient of Variation 16.4 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 159 µg/mL | Geometric Coefficient of Variation 15.7 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 165 µg/mL | Geometric Coefficient of Variation 17.4 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 151 µg/mL | Geometric Coefficient of Variation 17.4 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 128 µg/mL | Geometric Coefficient of Variation 66.1 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 144 µg/mL | Geometric Coefficient of Variation 18.3 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 144 µg/mL | Geometric Coefficient of Variation 18.5 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 146 µg/mL | Geometric Coefficient of Variation 44.2 |
Secondary
PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody
Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. Results are reported in mg\*hours (h)/mL.
Time frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose. The 'Number Analyzed' signifies participants evaluable for the specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | NA mg*h/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | NA mg*h/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | NA mg*h/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 16.1 mg*h/mL | Geometric Coefficient of Variation 2.34 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 20.6 mg*h/mL | Geometric Coefficient of Variation 22.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 17 mg*h/mL | Geometric Coefficient of Variation 13.9 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 21.6 mg*h/mL | Geometric Coefficient of Variation 37.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 24.2 mg*h/mL | Geometric Coefficient of Variation 31.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 36.1 mg*h/mL | Geometric Coefficient of Variation 23 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 22.7 mg*h/mL | Geometric Coefficient of Variation 14.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 24.5 mg*h/mL | Geometric Coefficient of Variation 31.4 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 18.6 mg*h/mL | Geometric Coefficient of Variation 22.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 18.4 mg*h/mL | Geometric Coefficient of Variation 22.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 23.5 mg*h/mL | Geometric Coefficient of Variation 34.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 22.8 mg*h/mL | Geometric Coefficient of Variation 24.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 34.7 mg*h/mL | Geometric Coefficient of Variation 49.3 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 17.5 mg*h/mL | Geometric Coefficient of Variation 19.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 25.8 mg*h/mL | Geometric Coefficient of Variation 22 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 39.2 mg*h/mL | Geometric Coefficient of Variation 20.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 22.3 mg*h/mL | Geometric Coefficient of Variation 16.7 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 14.8 mg*h/mL | Geometric Coefficient of Variation 13.8 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 18 mg*h/mL | Geometric Coefficient of Variation 22.2 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | NA mg*h/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 15.2 mg*h/mL | Geometric Coefficient of Variation 22.1 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 17.9 mg*h/mL | Geometric Coefficient of Variation 16.1 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 11.3 mg*h/mL | Geometric Coefficient of Variation 23 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 13.3 mg*h/mL | Geometric Coefficient of Variation 29 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 19.9 mg*h/mL | Geometric Coefficient of Variation 26.5 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 16.3 mg*h/mL | Geometric Coefficient of Variation 26.7 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 21.6 mg*h/mL | Geometric Coefficient of Variation 35.1 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 30 mg*h/mL | Geometric Coefficient of Variation 26 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | NA mg*h/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 14 mg*h/mL | Geometric Coefficient of Variation 23.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | NA mg*h/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 20.1 mg*h/mL | Geometric Coefficient of Variation 55 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 17.8 mg*h/mL | Geometric Coefficient of Variation 73.5 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 15.2 mg*h/mL | Geometric Coefficient of Variation 34.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | NA mg*h/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 17.4 mg*h/mL | Geometric Coefficient of Variation 19.4 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 29.1 mg*h/mL | Geometric Coefficient of Variation 33.6 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 16.4 mg*h/mL | Geometric Coefficient of Variation 14.1 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 24.8 mg*h/mL | Geometric Coefficient of Variation 26.2 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 16.2 mg*h/mL | Geometric Coefficient of Variation 33.1 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | NA mg*h/mL | — |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 12.1 mg*h/mL | Geometric Coefficient of Variation 19.1 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 16.8 mg*h/mL | Geometric Coefficient of Variation 16.3 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 14.4 mg*h/mL | Geometric Coefficient of Variation 32.1 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 20.2 mg*h/mL | Geometric Coefficient of Variation 28.2 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 17 mg*h/mL | Geometric Coefficient of Variation 30.5 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 18.4 mg*h/mL | Geometric Coefficient of Variation 49.1 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 20.1 mg*h/mL | Geometric Coefficient of Variation 29.7 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 28.9 mg*h/mL | Geometric Coefficient of Variation 55.2 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 20.9 mg*h/mL | Geometric Coefficient of Variation 30.8 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 20 mg*h/mL | Geometric Coefficient of Variation 44.6 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 16.9 mg*h/mL | Geometric Coefficient of Variation 32.9 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 17.8 mg*h/mL | Geometric Coefficient of Variation 26.3 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 35.8 mg*h/mL | Geometric Coefficient of Variation 32.6 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 25 mg*h/mL | Geometric Coefficient of Variation 25.4 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 19.7 mg*h/mL | Geometric Coefficient of Variation 20 |
Secondary
PK Parameter: AUCinf of Intact DM4 and SmDM4
Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. Note that '9999' is used because AUCinf cannot be calculated for n\<3.
Time frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose. The 'Number Analyzed' signifies participants evaluable for the specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | NA ng*h/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | NA ng*h/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | NA ng*h/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | NA ng*h/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | 282 ng*h/mL | Geometric Coefficient of Variation 14.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 1730 ng*h/mL | Geometric Coefficient of Variation 76.3 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 1700 ng*h/mL | Geometric Coefficient of Variation 51.5 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 249 ng*h/mL | Geometric Coefficient of Variation 12.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 1620 ng*h/mL | Geometric Coefficient of Variation 58.5 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 253 ng*h/mL | Geometric Coefficient of Variation 28.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | 263 ng*h/mL | Geometric Coefficient of Variation 31.4 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 1710 ng*h/mL | Geometric Coefficient of Variation 73.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | 315 ng*h/mL | Geometric Coefficient of Variation 36.5 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 289 ng*h/mL | Geometric Coefficient of Variation 30.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 1980 ng*h/mL | Geometric Coefficient of Variation 60.7 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 1930 ng*h/mL | Geometric Coefficient of Variation 52.9 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 2120 ng*h/mL | Geometric Coefficient of Variation 62.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | 285 ng*h/mL | Geometric Coefficient of Variation 27.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 2120 ng*h/mL | Geometric Coefficient of Variation 57.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 272 ng*h/mL | Geometric Coefficient of Variation 28.4 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 1370 ng*h/mL | Geometric Coefficient of Variation 49.2 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 1130 ng*h/mL | Geometric Coefficient of Variation 14.3 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 161 ng*h/mL | Geometric Coefficient of Variation 15.2 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | 146 ng*h/mL | Geometric Coefficient of Variation 22 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | NA ng*h/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 1600 ng*h/mL | Geometric Coefficient of Variation 49.6 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 202 ng*h/mL | Geometric Coefficient of Variation 21.6 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | 180 ng*h/mL | Geometric Coefficient of Variation 17.4 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 1600 ng*h/mL | Geometric Coefficient of Variation 52.4 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 2160 ng*h/mL | Geometric Coefficient of Variation 56.5 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 315 ng*h/mL | Geometric Coefficient of Variation 55.6 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | 295 ng*h/mL | Geometric Coefficient of Variation 31.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | NA ng*h/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 1510 ng*h/mL | Geometric Coefficient of Variation 63.7 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | NA ng*h/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 223 ng*h/mL | Geometric Coefficient of Variation 64.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 1660 ng*h/mL | Geometric Coefficient of Variation 119 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 1800 ng*h/mL | Geometric Coefficient of Variation 80.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | 200 ng*h/mL | Geometric Coefficient of Variation 24.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 180 ng*h/mL | Geometric Coefficient of Variation 19.7 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 2290 ng*h/mL | Geometric Coefficient of Variation 70 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | 289 ng*h/mL | Geometric Coefficient of Variation 53.6 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 1830 ng*h/mL | Geometric Coefficient of Variation 72.2 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 262 ng*h/mL | Geometric Coefficient of Variation 49.6 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | 163 ng*h/mL | Geometric Coefficient of Variation 7.42 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 2050 ng*h/mL | Geometric Coefficient of Variation 50 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | NA ng*h/mL | — |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 192 ng*h/mL | Geometric Coefficient of Variation 33.2 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 269 ng*h/mL | Geometric Coefficient of Variation 17.7 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | 245 ng*h/mL | Geometric Coefficient of Variation 29.7 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 2930 ng*h/mL | Geometric Coefficient of Variation 91.3 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 2280 ng*h/mL | Geometric Coefficient of Variation 61.9 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | 260 ng*h/mL | Geometric Coefficient of Variation 38.2 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 261 ng*h/mL | Geometric Coefficient of Variation 31.6 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 2080 ng*h/mL | Geometric Coefficient of Variation 75.5 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 2460 ng*h/mL | Geometric Coefficient of Variation 70.8 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 1830 ng*h/mL | Geometric Coefficient of Variation 61.2 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: AUCinf of Intact DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 1550 ng*h/mL | Geometric Coefficient of Variation 61.8 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 3 | 243 ng*h/mL | Geometric Coefficient of Variation 29.2 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: AUCinf of Intact DM4 and SmDM4 | DM4: Cycle 1 | 256 ng*h/mL | Geometric Coefficient of Variation 40.7 |
Secondary
PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody
Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles.
Time frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose. The 'Number Analyzed' signifies participants evaluable for the specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | NA mL/h | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | NA mL/h | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | NA mL/h | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 19.2 mL/h | Geometric Coefficient of Variation 18.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 15 mL/h | Geometric Coefficient of Variation 34.3 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 22 mL/h | Geometric Coefficient of Variation 17.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 16.9 mL/h | Geometric Coefficient of Variation 34.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 18 mL/h | Geometric Coefficient of Variation 23.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 11.7 mL/h | Geometric Coefficient of Variation 27.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 22 mL/h | Geometric Coefficient of Variation 29.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 17.5 mL/h | Geometric Coefficient of Variation 36.5 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 17.7 mL/h | Geometric Coefficient of Variation 23 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 20.9 mL/h | Geometric Coefficient of Variation 23.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 11.2 mL/h | Geometric Coefficient of Variation 43.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 16.5 mL/h | Geometric Coefficient of Variation 26.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 16.7 mL/h | Geometric Coefficient of Variation 33.9 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 18.3 mL/h | Geometric Coefficient of Variation 21.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 23.4 mL/h | Geometric Coefficient of Variation 23.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 16.3 mL/h | Geometric Coefficient of Variation 25.9 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 10.7 mL/h | Geometric Coefficient of Variation 26 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 16.3 mL/h | Geometric Coefficient of Variation 19.8 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | NA mL/h | — |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 19.3 mL/h | Geometric Coefficient of Variation 17.9 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 19.9 mL/h | Geometric Coefficient of Variation 10.1 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 18.2 mL/h | Geometric Coefficient of Variation 14 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 28.9 mL/h | Geometric Coefficient of Variation 17 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 24.5 mL/h | Geometric Coefficient of Variation 24.6 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 22 mL/h | Geometric Coefficient of Variation 26.1 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 16.6 mL/h | Geometric Coefficient of Variation 36.1 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 17.2 mL/h | Geometric Coefficient of Variation 24.9 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 11.1 mL/h | Geometric Coefficient of Variation 20.5 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | NA mL/h | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | NA mL/h | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 21.2 mL/h | Geometric Coefficient of Variation 22.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 14.7 mL/h | Geometric Coefficient of Variation 47.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 19.3 mL/h | Geometric Coefficient of Variation 83.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 20.3 mL/h | Geometric Coefficient of Variation 23.9 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | NA mL/h | — |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 23.3 mL/h | Geometric Coefficient of Variation 38.6 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 15.7 mL/h | Geometric Coefficient of Variation 34.6 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 13.9 mL/h | Geometric Coefficient of Variation 40.5 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 24.3 mL/h | Geometric Coefficient of Variation 21.4 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 24.5 mL/h | Geometric Coefficient of Variation 41.3 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 26.4 mL/h | Geometric Coefficient of Variation 25 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 21.1 mL/h | Geometric Coefficient of Variation 15.2 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | NA mL/h | — |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 29.2 mL/h | Geometric Coefficient of Variation 17.1 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 18.3 mL/h | Geometric Coefficient of Variation 36.8 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 23.9 mL/h | Geometric Coefficient of Variation 34.5 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 22.6 mL/h | Geometric Coefficient of Variation 49.2 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 16.4 mL/h | Geometric Coefficient of Variation 63.9 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 12.9 mL/h | Geometric Coefficient of Variation 57.5 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 17.7 mL/h | Geometric Coefficient of Variation 35.6 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 20 mL/h | Geometric Coefficient of Variation 44.7 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 22.8 mL/h | Geometric Coefficient of Variation 34.5 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 3 | 19.2 mL/h | Geometric Coefficient of Variation 23.6 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 1 | 16.1 mL/h | Geometric Coefficient of Variation 26.7 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Total Antibody: Cycle 3 | 9.69 mL/h | Geometric Coefficient of Variation 38.1 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody | Mirvetuximab Soravtansine: Cycle 1 | 22.1 mL/h | Geometric Coefficient of Variation 26.8 |
Secondary
PK Parameter: CL of DM4 and SmDM4
Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles.
Time frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose. The 'Number Analyzed' signifies participants evaluable for the specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | NA L/h | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | NA L/h | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | NA L/h | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | NA L/h | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 4.49 L/h | Geometric Coefficient of Variation 40.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 4.18 L/h | Geometric Coefficient of Variation 66.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | 23.5 L/h | Geometric Coefficient of Variation 26.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 29 L/h | Geometric Coefficient of Variation 19.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 4.77 L/h | Geometric Coefficient of Variation 61.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 4.97 L/h | Geometric Coefficient of Variation 48.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 30.9 L/h | Geometric Coefficient of Variation 31.5 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | 28.9 L/h | Geometric Coefficient of Variation 33 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | 22.7 L/h | Geometric Coefficient of Variation 39.7 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 3.84 L/h | Geometric Coefficient of Variation 57.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 25.2 L/h | Geometric Coefficient of Variation 36.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 3.84 L/h | Geometric Coefficient of Variation 50.5 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 3.87 L/h | Geometric Coefficient of Variation 52.7 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 28.6 L/h | Geometric Coefficient of Variation 33.3 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 3.82 L/h | Geometric Coefficient of Variation 60.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | 27.2 L/h | Geometric Coefficient of Variation 35.5 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 35 L/h | Geometric Coefficient of Variation 14.6 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | 38.6 L/h | Geometric Coefficient of Variation 16 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 4.39 L/h | Geometric Coefficient of Variation 52 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 5.19 L/h | Geometric Coefficient of Variation 20.3 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | 34.5 L/h | Geometric Coefficient of Variation 23.4 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | NA L/h | — |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 30.7 L/h | Geometric Coefficient of Variation 26.8 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 4.19 L/h | Geometric Coefficient of Variation 48.3 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 3.35 L/h | Geometric Coefficient of Variation 70.6 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 4.26 L/h | Geometric Coefficient of Variation 59 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | 22.1 L/h | Geometric Coefficient of Variation 45.8 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 21.8 L/h | Geometric Coefficient of Variation 64.7 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 25.1 L/h | Geometric Coefficient of Variation 59.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | NA L/h | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | NA L/h | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 3.9 L/h | Geometric Coefficient of Variation 59.6 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 3.9 L/h | Geometric Coefficient of Variation 83.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | 33.5 L/h | Geometric Coefficient of Variation 41.5 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 4.21 L/h | Geometric Coefficient of Variation 119 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 37.4 L/h | Geometric Coefficient of Variation 28.3 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 3.45 L/h | Geometric Coefficient of Variation 56.3 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | 26.6 L/h | Geometric Coefficient of Variation 54.3 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 28.2 L/h | Geometric Coefficient of Variation 52.2 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 4.17 L/h | Geometric Coefficient of Variation 62.8 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 35.5 L/h | Geometric Coefficient of Variation 57.2 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | 44.6 L/h | Geometric Coefficient of Variation 22.3 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | NA L/h | — |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 3.42 L/h | Geometric Coefficient of Variation 73 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 3.22 L/h | Geometric Coefficient of Variation 81.9 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | 28.8 L/h | Geometric Coefficient of Variation 44.4 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 28.8 L/h | Geometric Coefficient of Variation 30.7 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 2.78 L/h | Geometric Coefficient of Variation 91.8 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 3.57 L/h | Geometric Coefficient of Variation 63.9 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 3.06 L/h | Geometric Coefficient of Variation 63.2 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 27.7 L/h | Geometric Coefficient of Variation 27.5 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | 26.7 L/h | Geometric Coefficient of Variation 31.8 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 3 | 29.5 L/h | Geometric Coefficient of Variation 31.5 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 1 | 4.25 L/h | Geometric Coefficient of Variation 57.1 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: CL of DM4 and SmDM4 | DM4: Cycle 1 | 29.1 L/h | Geometric Coefficient of Variation 40.4 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: CL of DM4 and SmDM4 | S-methyl DM4: Cycle 3 | 4.78 L/h | Geometric Coefficient of Variation 60.4 |
Secondary
PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4)
Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. Results are reported in nanograms (ng)/mL.
Time frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of end of infusion [EOI], and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose. The 'Number Analyzed' signifies participants evaluable for the specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 3.61 ng/mL | Geometric Coefficient of Variation 26.7 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | NA ng/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 3.04 ng/mL | Geometric Coefficient of Variation 21.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | NA ng/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | 12.3 ng/mL | Geometric Coefficient of Variation 71.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 9.6 ng/mL | Geometric Coefficient of Variation 65.5 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 4.71 ng/mL | Geometric Coefficient of Variation 32.9 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | 5.06 ng/mL | Geometric Coefficient of Variation 30.5 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | 4.57 ng/mL | Geometric Coefficient of Variation 27.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 5.51 ng/mL | Geometric Coefficient of Variation 35.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | 11.8 ng/mL | Geometric Coefficient of Variation 55.7 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 11.5 ng/mL | Geometric Coefficient of Variation 61.7 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | 6.16 ng/mL | Geometric Coefficient of Variation 43.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | 12.2 ng/mL | Geometric Coefficient of Variation 51.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 12.2 ng/mL | Geometric Coefficient of Variation 68.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 6.32 ng/mL | Geometric Coefficient of Variation 33.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 12.2 ng/mL | Geometric Coefficient of Variation 62.6 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 5.59 ng/mL | Geometric Coefficient of Variation 37.5 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | 5.45 ng/mL | Geometric Coefficient of Variation 69.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | 12.5 ng/mL | Geometric Coefficient of Variation 89.2 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | 3.21 ng/mL | Geometric Coefficient of Variation 220 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | 3.06 ng/mL | Geometric Coefficient of Variation 23.4 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 2.96 ng/mL | Geometric Coefficient of Variation 8.85 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 5.75 ng/mL | Geometric Coefficient of Variation 56.3 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 3.72 ng/mL | Geometric Coefficient of Variation 28.7 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | 6.79 ng/mL | Geometric Coefficient of Variation 59.1 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 7.91 ng/mL | Geometric Coefficient of Variation 46.9 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | 3.38 ng/mL | Geometric Coefficient of Variation 15 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | 14.1 ng/mL | Geometric Coefficient of Variation 43.9 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 6.4 ng/mL | Geometric Coefficient of Variation 27.7 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 13 ng/mL | Geometric Coefficient of Variation 37.5 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | 5.66 ng/mL | Geometric Coefficient of Variation 31.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 7.23 ng/mL | Geometric Coefficient of Variation 50.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | NA ng/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | NA ng/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 4.12 ng/mL | Geometric Coefficient of Variation 47.5 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 3.93 ng/mL | Geometric Coefficient of Variation 18.3 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | 5.1 ng/mL | Geometric Coefficient of Variation 34.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | 10.8 ng/mL | Geometric Coefficient of Variation 55.7 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 7.51 ng/mL | Geometric Coefficient of Variation 58.1 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | 7.02 ng/mL | Geometric Coefficient of Variation 70.8 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 6.58 ng/mL | Geometric Coefficient of Variation 86.4 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | 17.6 ng/mL | Geometric Coefficient of Variation 63 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 11.9 ng/mL | Geometric Coefficient of Variation 77.1 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | 16.2 ng/mL | Geometric Coefficient of Variation 11.1 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 11.3 ng/mL | Geometric Coefficient of Variation 56.6 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 4.54 ng/mL | Geometric Coefficient of Variation 49.3 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | 3.91 ng/mL | Geometric Coefficient of Variation 5.81 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 17 ng/mL | Geometric Coefficient of Variation 91.8 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | 4.91 ng/mL | Geometric Coefficient of Variation 37.3 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 5.6 ng/mL | Geometric Coefficient of Variation 31.2 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | 18 ng/mL | Geometric Coefficient of Variation 52.9 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 12.8 ng/mL | Geometric Coefficient of Variation 63.6 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | 13 ng/mL | Geometric Coefficient of Variation 71.6 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | 4.95 ng/mL | Geometric Coefficient of Variation 33.3 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 5.27 ng/mL | Geometric Coefficient of Variation 35.3 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 3 | 9.49 ng/mL | Geometric Coefficient of Variation 104 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 3 | 4.44 ng/mL | Geometric Coefficient of Variation 25.7 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | DM4: Cycle 1 | 4.52 ng/mL | Geometric Coefficient of Variation 38.4 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) | S-methyl DM4: Cycle 1 | 8.64 ng/mL | Geometric Coefficient of Variation 71.7 |
Secondary
PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4
Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. PK parameters were calculated using standard non-compartmental methods. The terminal t½ is an estimate (extrapolation) of the time it takes for the concentration or amount in the body of that drug to be reduced by exactly one-half (50%). If extrapolated AUC was greater than 20% (due to insufficient number of participants with data samples) the upper range of t½ was not reported.
Time frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (up to 336 hours) (additionally at Day 22 for Regimen C)
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose. The 'Number Analyzed' signifies participants evaluable for the specified categories.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 142 h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 104 h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 49.9 h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 74.4 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 132 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 206 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 132 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 235 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 123 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 83.8 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 128 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 73.9 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 126 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 182 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 124 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 214 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 70.2 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 132 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 132 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 128 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 121 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 221 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 228 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 61.9 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 71.1 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 129 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 126 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 130 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 216 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 121 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 78.3 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 139 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 200 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 126 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 63.9 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 128 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 189 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 214 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 124 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 117 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 59.4 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 68 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 140 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 170 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 124 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 123 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 168 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 63.6 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 290 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 60.6 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 128 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 137 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 52.4 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 208 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 132 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 74.1 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 124 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 214 h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 168 h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 65.9 h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 231 h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 124 h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 175 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 96 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 337 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 182 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 148 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 55.8 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 181 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 282 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 119 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 230 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 64.4 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 154 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 169 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 137 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 249 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 57.4 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 120 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 171 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 46.4 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 184 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 197 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 132 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 46.5 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 114 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 126 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 64.6 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 148 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 269 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 182 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 132 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 73.6 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 134 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 126 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 127 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 133 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 59.4 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 140 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 64 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 232 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 196 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 122 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 126 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 57.5 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 140 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 63 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 251 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 215 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 138 h |
Secondary
PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4
Blood samples from participants were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles. PK parameters were derived using non-compartmental PK analysis.
Time frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (up to 336 hours) (additionally at Day 22 for Regimen C)
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose. The 'Number Analyzed' signifies participants evaluable for the specified categories.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 1.75 h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.2 h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 23.8 h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 1.75 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.5 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 1.9 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 1.9 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 3.88 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 3.88 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 7.01 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 23.9 h |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 7 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.78 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 7.17 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 7.06 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 2.1 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 2.1 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 3.68 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 3.46 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 7.83 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 2.24 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 1.92 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 6.94 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 7.11 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 2.24 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 1.9 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.63 h |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 7.83 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 2.05 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 8.26 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 2.06 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 6.96 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 1.49 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.58 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 7.41 h |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 1.49 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 6.99 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.4 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 6.99 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 1.68 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 48.2 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 1.68 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 6.91 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 4.06 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 1.02 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 4.09 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 108 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 15.1 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.56 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 1.96 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 6.96 h |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 1.03 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 7.34 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 1.48 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 6.08 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 1.48 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 1.88 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.34 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 6.08 h |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 1.86 h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 4.28 h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.12 h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 23.8 h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 3.84 h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | NA h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 1.23 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 7.04 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 1.73 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 1.87 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 4.04 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.32 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 6.89 h |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 23.8 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 7.02 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 5.98 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 5.98 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 6.08 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 7.7 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 7.02 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 5.98 h |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 7.12 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 1.45 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 4.82 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 2 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 7.1 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 7.72 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 7.1 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 7.1 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.62 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 1.26 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 7.08 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 2.14 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 7.08 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 2.25 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 3.7 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 7.84 h |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.7 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 7.12 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 1.63 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 7.03 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 8 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 2.08 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 2.12 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.58 h |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 1.5 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 1 | 2.2 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 3 | 7.13 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody: Cycle 3 | 3.03 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 1 | 2.07 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 3 | 7.22 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | S-methyl DM4: Cycle 1 | 8.15 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine: Cycle 3 | 6.98 h |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4: Cycle 1 | 7.67 h |
Secondary
PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4
Blood samples from participants were analyzed to characterize PK when administered in 3- or 4-week cycles.
Time frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose. The 'Number Analyzed' signifies participants evaluable for the specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | NA L | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 2.93 L | Geometric Coefficient of Variation 18.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | NA L | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | NA L | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | NA L | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | NA L | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | NA L | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | NA L | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | 3.74 L | Geometric Coefficient of Variation 23.7 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 3.63 L | Geometric Coefficient of Variation 12.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | 761 L | Geometric Coefficient of Variation 53.6 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | 3.21 L | Geometric Coefficient of Variation 14.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | 911 L | Geometric Coefficient of Variation 57.3 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | 2190 L | Geometric Coefficient of Variation 20.7 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 2590 L | Geometric Coefficient of Variation 23.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 4.38 L | Geometric Coefficient of Variation 16.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | 3.25 L | Geometric Coefficient of Variation 13.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 4.05 L | Geometric Coefficient of Variation 22.7 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | 3.17 L | Geometric Coefficient of Variation 17.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | 2480 L | Geometric Coefficient of Variation 24.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | 878 L | Geometric Coefficient of Variation 48.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 3.54 L | Geometric Coefficient of Variation 19.7 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | 900 L | Geometric Coefficient of Variation 67.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 2490 L | Geometric Coefficient of Variation 31.4 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 2010 L | Geometric Coefficient of Variation 38.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | 2.97 L | Geometric Coefficient of Variation 34.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | 698 L | Geometric Coefficient of Variation 51.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 3.9 L | Geometric Coefficient of Variation 34.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | 731 L | Geometric Coefficient of Variation 69.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 3.31 L | Geometric Coefficient of Variation 18.5 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | 1990 L | Geometric Coefficient of Variation 43.7 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | 2.83 L | Geometric Coefficient of Variation 23.3 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 4.06 L | Geometric Coefficient of Variation 23.9 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | 696 L | Geometric Coefficient of Variation 51 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | 2370 L | Geometric Coefficient of Variation 35.9 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | 2.95 L | Geometric Coefficient of Variation 24.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 3.87 L | Geometric Coefficient of Variation 25.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 2240 L | Geometric Coefficient of Variation 40.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | 3.23 L | Geometric Coefficient of Variation 23.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | 751 L | Geometric Coefficient of Variation 66.7 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | 932 L | Geometric Coefficient of Variation 63.7 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 3.23 L | Geometric Coefficient of Variation 7.04 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 4.03 L | Geometric Coefficient of Variation 28.1 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | NA L | — |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | 1100 L | Geometric Coefficient of Variation 1.87 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | 3.37 L | Geometric Coefficient of Variation 13.3 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 2670 L | Geometric Coefficient of Variation 20.9 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | 3030 L | Geometric Coefficient of Variation 7.84 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 5.67 L | Geometric Coefficient of Variation 10.7 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | 3160 L | Geometric Coefficient of Variation 7.05 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 4.29 L | Geometric Coefficient of Variation 11.9 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | NA L | — |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | 833 L | Geometric Coefficient of Variation 24.5 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | 3.4 L | Geometric Coefficient of Variation 15.7 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 2580 L | Geometric Coefficient of Variation 59.4 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | 3.09 L | Geometric Coefficient of Variation 8.55 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | 1900 L | Geometric Coefficient of Variation 55.6 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | 3.13 L | Geometric Coefficient of Variation 12.5 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | 652 L | Geometric Coefficient of Variation 65 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 1720 L | Geometric Coefficient of Variation 36 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 4.27 L | Geometric Coefficient of Variation 24.4 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 3.52 L | Geometric Coefficient of Variation 23.3 |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | 754 L | Geometric Coefficient of Variation 60.7 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | 832 L | Geometric Coefficient of Variation 61.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | NA L | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | NA L | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 4.48 L | Geometric Coefficient of Variation 39.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | NA L | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | NA L | — |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 3.69 L | Geometric Coefficient of Variation 17.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 1880 L | Geometric Coefficient of Variation 51.6 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | 3.78 L | Geometric Coefficient of Variation 16.6 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 3.8 L | Geometric Coefficient of Variation 10.7 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 5.01 L | Geometric Coefficient of Variation 1.58 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | 3300 L | Geometric Coefficient of Variation 38.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 2730 L | Geometric Coefficient of Variation 26.5 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | NA L | — |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | 947 L | Geometric Coefficient of Variation 82.5 |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | 1100 L | Geometric Coefficient of Variation 114 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | 2140 L | Geometric Coefficient of Variation 35.9 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | 855 L | Geometric Coefficient of Variation 66.3 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 4.09 L | Geometric Coefficient of Variation 17.2 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 2010 L | Geometric Coefficient of Variation 53.5 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | 3.98 L | Geometric Coefficient of Variation 19 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 3.88 L | Geometric Coefficient of Variation 24.1 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | 3.76 L | Geometric Coefficient of Variation 49.6 |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | 773 L | Geometric Coefficient of Variation 64.7 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | 695 L | Geometric Coefficient of Variation 81.2 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | NA L | — |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | NA L | — |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | 2930 L | Geometric Coefficient of Variation 22.9 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 4.58 L | Geometric Coefficient of Variation 20.9 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 2100 L | Geometric Coefficient of Variation 80.9 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 5.33 L | Geometric Coefficient of Variation 18.7 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | 3.94 L | Geometric Coefficient of Variation 15.4 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | 621 L | Geometric Coefficient of Variation 76.2 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 2410 L | Geometric Coefficient of Variation 52.5 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | 4.01 L | Geometric Coefficient of Variation 57.5 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 3.78 L | Geometric Coefficient of Variation 21.8 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | 547 L | Geometric Coefficient of Variation 97.6 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | 3.28 L | Geometric Coefficient of Variation 31 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | 2450 L | Geometric Coefficient of Variation 53.6 |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 4.69 L | Geometric Coefficient of Variation 23 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | 3.28 L | Geometric Coefficient of Variation 30.5 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 2060 L | Geometric Coefficient of Variation 31.1 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | 3.1 L | Geometric Coefficient of Variation 25.8 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | 709 L | Geometric Coefficient of Variation 59.1 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | 2270 L | Geometric Coefficient of Variation 32.8 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 4.09 L | Geometric Coefficient of Variation 30.1 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 3.59 L | Geometric Coefficient of Variation 23.1 |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | 592 L | Geometric Coefficient of Variation 66.4 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 1 | 3.73 L | Geometric Coefficient of Variation 23 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 1 | 2350 L | Geometric Coefficient of Variation 45.1 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 1 | 840 L | Geometric Coefficient of Variation 65.1 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 3 | 2.9 L | Geometric Coefficient of Variation 25.4 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | DM4 Cycle 3 | 2450 L | Geometric Coefficient of Variation 29.1 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Total Antibody Cycle 1 | 4.21 L | Geometric Coefficient of Variation 25.6 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | Mirvetuximab Soravtansine Cycle 3 | 3.51 L | Geometric Coefficient of Variation 21.6 |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 | SmDM4 Cycle 3 | 891 L | Geometric Coefficient of Variation 67.2 |
Secondary
Plasma Concentration of Bevacizumab
Blood samples from participants at the end of infusion were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles.
Time frame: At end of infusion (EOI) of Cycle 1; and at pre-infusion and EOI of Cycles 2 to 6
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose. The 'Number Analyzed' signifies participants evaluable for the specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 4 EOI | NA ug/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 3 EOI | NA ug/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 6 EOI | NA ug/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 5 EOI | NA ug/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 4 Pre-infusion | NA ug/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 2 Pre-infusion | 69.3 ug/mL | Geometric Coefficient of Variation 37 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 1 EOI | 368 ug/mL | Geometric Coefficient of Variation 20.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 2 EOI | NA ug/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 3 Pre-infusion | NA ug/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 5 Pre-infusion | NA ug/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 6 Pre-infusion | NA ug/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 6 Pre-infusion | 80.7 ug/mL | Geometric Coefficient of Variation 96.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 4 EOI | 537 ug/mL | Geometric Coefficient of Variation 25.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 3 Pre-infusion | 79.9 ug/mL | Geometric Coefficient of Variation 52.9 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 3 EOI | 408 ug/mL | Geometric Coefficient of Variation 59.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 2 EOI | 477 ug/mL | Geometric Coefficient of Variation 23.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 6 EOI | 513 ug/mL | Geometric Coefficient of Variation 29.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 5 EOI | 583 ug/mL | Geometric Coefficient of Variation 31.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 5 Pre-infusion | 134 ug/mL | Geometric Coefficient of Variation 18.3 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 1 EOI | 352 ug/mL | Geometric Coefficient of Variation 31.9 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 4 Pre-infusion | 133 ug/mL | Geometric Coefficient of Variation 24.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Bevacizumab | Cycle 2 Pre-infusion | 66 ug/mL | Geometric Coefficient of Variation 35.4 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Bevacizumab | Cycle 4 Pre-infusion | 134 ug/mL | Geometric Coefficient of Variation 51.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Bevacizumab | Cycle 5 Pre-infusion | 163 ug/mL | Geometric Coefficient of Variation 28.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Bevacizumab | Cycle 4 EOI | 539 ug/mL | Geometric Coefficient of Variation 20.7 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Bevacizumab | Cycle 2 Pre-infusion | 90.6 ug/mL | Geometric Coefficient of Variation 57.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Bevacizumab | Cycle 1 EOI | 406 ug/mL | Geometric Coefficient of Variation 22.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Bevacizumab | Cycle 2 EOI | 429 ug/mL | Geometric Coefficient of Variation 38.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Bevacizumab | Cycle 6 Pre-infusion | 191 ug/mL | Geometric Coefficient of Variation 27.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Bevacizumab | Cycle 3 Pre-infusion | 132 ug/mL | Geometric Coefficient of Variation 17 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Bevacizumab | Cycle 6 EOI | 574 ug/mL | Geometric Coefficient of Variation 26.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Bevacizumab | Cycle 5 EOI | 565 ug/mL | Geometric Coefficient of Variation 19.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Bevacizumab | Cycle 3 EOI | 540 ug/mL | Geometric Coefficient of Variation 23.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 6 Pre-infusion | 149 ug/mL | Geometric Coefficient of Variation 37.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 1 EOI | 430 ug/mL | Geometric Coefficient of Variation 19.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 2 Pre-infusion | 87.5 ug/mL | Geometric Coefficient of Variation 37.4 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 2 EOI | 528 ug/mL | Geometric Coefficient of Variation 20.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 3 Pre-infusion | 117 ug/mL | Geometric Coefficient of Variation 39.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 3 EOI | 556 ug/mL | Geometric Coefficient of Variation 17.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 4 Pre-infusion | 141 ug/mL | Geometric Coefficient of Variation 49.4 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 4 EOI | 505 ug/mL | Geometric Coefficient of Variation 39.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 5 Pre-infusion | 151 ug/mL | Geometric Coefficient of Variation 36.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 5 EOI | 587 ug/mL | Geometric Coefficient of Variation 20.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 6 EOI | 559 ug/mL | Geometric Coefficient of Variation 23.9 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 5 Pre-infusion | 137 ug/mL | Geometric Coefficient of Variation 61 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 2 EOI | 559 ug/mL | Geometric Coefficient of Variation 28.4 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 6 EOI | 654 ug/mL | Geometric Coefficient of Variation 24.6 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 6 Pre-infusion | 166 ug/mL | Geometric Coefficient of Variation 29.6 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 5 EOI | 558 ug/mL | Geometric Coefficient of Variation 80.6 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 2 Pre-infusion | 88.1 ug/mL | Geometric Coefficient of Variation 35 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 3 EOI | 616 ug/mL | Geometric Coefficient of Variation 22.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 1 EOI | 448 ug/mL | Geometric Coefficient of Variation 23.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 3 Pre-infusion | 118 ug/mL | Geometric Coefficient of Variation 51.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 4 EOI | 584 ug/mL | Geometric Coefficient of Variation 35.7 |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Plasma Concentration of Bevacizumab | Cycle 4 Pre-infusion | 123 ug/mL | Geometric Coefficient of Variation 78.2 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Plasma Concentration of Bevacizumab | Cycle 4 Pre-infusion | 132 ug/mL | Geometric Coefficient of Variation 92.9 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Plasma Concentration of Bevacizumab | Cycle 6 EOI | 525 ug/mL | Geometric Coefficient of Variation 39.8 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Plasma Concentration of Bevacizumab | Cycle 5 Pre-infusion | 153 ug/mL | Geometric Coefficient of Variation 51 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Plasma Concentration of Bevacizumab | Cycle 3 EOI | 531 ug/mL | Geometric Coefficient of Variation 33.1 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Plasma Concentration of Bevacizumab | Cycle 3 Pre-infusion | 127 ug/mL | Geometric Coefficient of Variation 45.8 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Plasma Concentration of Bevacizumab | Cycle 5 EOI | 547 ug/mL | Geometric Coefficient of Variation 24.1 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Plasma Concentration of Bevacizumab | Cycle 2 EOI | 473 ug/mL | Geometric Coefficient of Variation 44.6 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Plasma Concentration of Bevacizumab | Cycle 2 Pre-infusion | 92.5 ug/mL | Geometric Coefficient of Variation 39.9 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Plasma Concentration of Bevacizumab | Cycle 6 Pre-infusion | 170 ug/mL | Geometric Coefficient of Variation 51.5 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Plasma Concentration of Bevacizumab | Cycle 1 EOI | 413 ug/mL | Geometric Coefficient of Variation 23.9 |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Plasma Concentration of Bevacizumab | Cycle 4 EOI | 485 ug/mL | Geometric Coefficient of Variation 128 |
Secondary
Plasma Concentration of Carboplatin
Blood samples from participants at the end of infusion were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles.
Time frame: At end of infusion, 6 and 24 hours post-infusion of Cycle 1; and at pre-infusion and end of infusion of Cycles 2, 4, 5 and 6; at pre-infusion, end of infusion and 6 and 24 hours post-infusion of Cycle 3
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose. The 'Number Analyzed' signifies participants evaluable for the specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 1 24 hours post-infusion | 719 ng/mL | Geometric Coefficient of Variation 4.77 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 4: Pre-infusion | 220 ng/mL | Geometric Coefficient of Variation 31.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 5: Pre-infusion | 199 ng/mL | Geometric Coefficient of Variation 41.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 4: EOI | 8230 ng/mL | Geometric Coefficient of Variation 43.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 1: EOI | 10300 ng/mL | Geometric Coefficient of Variation 11.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 2: Pre-infusion | 124 ng/mL | Geometric Coefficient of Variation 14.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 6: EOI | 12100 ng/mL | Geometric Coefficient of Variation 32.5 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 2: EOI | 10800 ng/mL | Geometric Coefficient of Variation 22 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 1: 6 hours post-infusion | 2890 ng/mL | Geometric Coefficient of Variation 45.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 3: Pre-infusion | NA ng/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 6: Pre-infusion | 251 ng/mL | Geometric Coefficient of Variation 20.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 3: EOI | NA ng/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 5: EOI | 10900 ng/mL | Geometric Coefficient of Variation 36.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 3: 6 hours post-infusion | 1140 ng/mL | Geometric Coefficient of Variation 412 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 3: 24 hours post-infusion | NA ng/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 3: Pre-infusion | 245 ng/mL | Geometric Coefficient of Variation 34.6 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 3: 24 hours post-infusion | 1330 ng/mL | Geometric Coefficient of Variation 27.3 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 1 24 hours post-infusion | 913 ng/mL | Geometric Coefficient of Variation 19.7 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 5: Pre-infusion | NA ng/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 1: 6 hours post-infusion | 3790 ng/mL | Geometric Coefficient of Variation 10.3 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 4: Pre-infusion | 243 ng/mL | Geometric Coefficient of Variation 59.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 5: EOI | NA ng/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 2: EOI | 11600 ng/mL | Geometric Coefficient of Variation 18.5 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 1: EOI | 1060 ng/mL | Geometric Coefficient of Variation 35.2 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 4: EOI | NA ng/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 6: Pre-infusion | NA ng/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 6: EOI | NA ng/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 3: 6 hours post-infusion | 3890 ng/mL | Geometric Coefficient of Variation 29.9 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 2: Pre-infusion | 142 ng/mL | Geometric Coefficient of Variation 21.7 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Carboplatin | Cycle 3: EOI | 4170 ng/mL | Geometric Coefficient of Variation 946 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 4: Pre-infusion | 214 ng/mL | Geometric Coefficient of Variation 20.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 1: EOI | 13900 ng/mL | Geometric Coefficient of Variation 19 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 1: 6 hours post-infusion | 3120 ng/mL | Geometric Coefficient of Variation 151 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 1 24 hours post-infusion | 1030 ng/mL | Geometric Coefficient of Variation 43.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 2: Pre-infusion | 158 ng/mL | Geometric Coefficient of Variation 13.5 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 2: EOI | 11700 ng/mL | Geometric Coefficient of Variation 80.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 3: Pre-infusion | 173 ng/mL | Geometric Coefficient of Variation 35.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 3: EOI | 12100 ng/mL | Geometric Coefficient of Variation 28.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 3: 6 hours post-infusion | 1630 ng/mL | Geometric Coefficient of Variation 238 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 3: 24 hours post-infusion | 1270 ng/mL | Geometric Coefficient of Variation 41.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 4: EOI | 214 ng/mL | Geometric Coefficient of Variation 20.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 5: Pre-infusion | 194 ng/mL | Geometric Coefficient of Variation 37.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 5: EOI | 13800 ng/mL | Geometric Coefficient of Variation 31.8 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 6: Pre-infusion | 234 ng/mL | Geometric Coefficient of Variation 24.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Carboplatin | Cycle 6: EOI | 12100 ng/mL | Geometric Coefficient of Variation 32.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Carboplatin | Cycle 5: Pre-infusion | 270 ng/mL | Geometric Coefficient of Variation 43 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Carboplatin | Cycle 3: EOI | 12300 ng/mL | Geometric Coefficient of Variation 26.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Carboplatin | Cycle 1: EOI | 11800 ng/mL | Geometric Coefficient of Variation 25.6 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Carboplatin | Cycle 5: EOI | 11200 ng/mL | Geometric Coefficient of Variation 88.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Carboplatin | Cycle 3: Pre-infusion | 203 ng/mL | Geometric Coefficient of Variation 28.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Carboplatin | Cycle 2: EOI | 11000 ng/mL | Geometric Coefficient of Variation 146 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Carboplatin | Cycle 6: EOI | 10700 ng/mL | Geometric Coefficient of Variation 77.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Carboplatin | Cycle 6: Pre-infusion | 271 ng/mL | Geometric Coefficient of Variation 45.4 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Carboplatin | Cycle 2: Pre-infusion | 170 ng/mL | Geometric Coefficient of Variation 79.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Carboplatin | Cycle 4: EOI | 12500 ng/mL | Geometric Coefficient of Variation 29.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Carboplatin | Cycle 4: Pre-infusion | 250 ng/mL | Geometric Coefficient of Variation 39.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Carboplatin | Cycle 3: 24 hours post-infusion | 1440 ng/mL | Geometric Coefficient of Variation 49 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Plasma Concentration of Carboplatin | Cycle 1 24 hours post-infusion | 817 ng/mL | Geometric Coefficient of Variation 35 |
Secondary
Plasma Concentration of Pegylated Liposomal Doxorubicin
Blood samples from participants at the end of infusion were analyzed to characterize the PK of mirvetuximab soravtansine when administered in 3- or 4-week cycles.
Time frame: At end of infusion of Cycle 1; and at pre-infusion and end of infusion of Cycles 2 to 6
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose. The 'Number Analyzed' signifies participants evaluable for the specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 4: EOI | NA ng/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 3: Pre-infusion | NA ng/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 5: EOI | NA ng/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 1: EOI | 18700 ng/mL | Geometric Coefficient of Variation 8.72 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 3: EOI | NA ng/mL | — |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 2: EOI | 17300 ng/mL | Geometric Coefficient of Variation 17.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 6: EOI | NA ng/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 4: Pre-infusion | NA ng/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 1: EOI | 24400 ng/mL | Geometric Coefficient of Variation 14.3 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 2: Pre-infusion | NA ng/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 2: EOI | 25700 ng/mL | Geometric Coefficient of Variation 6.88 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 3: Pre-infusion | NA ng/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 3: EOI | 26200 ng/mL | Geometric Coefficient of Variation 12.8 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 4: EOI | 24300 ng/mL | Geometric Coefficient of Variation 24.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 5: Pre-infusion | NA ng/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 5: EOI | 23700 ng/mL | Geometric Coefficient of Variation 17.1 |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 6: Pre-infusion | NA ng/mL | — |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 6: EOI | 22900 ng/mL | Geometric Coefficient of Variation 13.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 4: EOI | 24400 ng/mL | Geometric Coefficient of Variation 15.4 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 6: Pre-infusion | 157 ng/mL | Geometric Coefficient of Variation 134 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 5: Pre-infusion | 177 ng/mL | Geometric Coefficient of Variation 81.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 2: Pre-infusion | 226 ng/mL | Geometric Coefficient of Variation 44.9 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 1: EOI | 26400 ng/mL | Geometric Coefficient of Variation 7.85 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 5: EOI | 25000 ng/mL | Geometric Coefficient of Variation 11.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 3: EOI | 26200 ng/mL | Geometric Coefficient of Variation 14.3 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 3: Pre-infusion | 228 ng/mL | Geometric Coefficient of Variation 63 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 4: Pre-infusion | 151 ng/mL | Geometric Coefficient of Variation 54.2 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 2: EOI | 26100 ng/mL | Geometric Coefficient of Variation 12.1 |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Plasma Concentration of Pegylated Liposomal Doxorubicin | Cycle 6: EOI | 24600 ng/mL | Geometric Coefficient of Variation 14.7 |
Secondary
Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1
PFS was defined as the time from the date of the first dose of study drug until the date of PD or death from any cause, whichever occurred first, estimated using the Kaplan-Meier method. PFS was defined based on radiological assessments and determined by the investigator. PD was defined as at least a 20% increase in the SLD of target lesions, taking as reference the smallest (nadir) SLD since and including baseline. In addition to the relative increase of 20%, the SLD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Time frame: From first dose of study drug until the date of PD or death by any cause (maximum exposure: 238.3 weeks)
Population: Response-Evaluable Population: All participants who received at least 1 dose of study treatment, had radiographic assessment at baseline received at least 1 dose of combination treatment, and at least 1 post-dose radiographic tumor assessment or have died within 105 days of first dose.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mirvetuximab Soravtansine 5 mg/kg + Bevacizumab 15 mg/kg | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 13.49 months |
| Mirvetuximab Soravtansine 6 mg/kg + Bevacizumab 15 mg/kg | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 8.80 months |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC4 | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 9.92 months |
| Mirvetuximab Soravtansine 5 mg/kg + Carboplatin AUC5 | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 6.77 months |
| Mirvetuximab Soravtansine 6 mg/kg + Carboplatin AUC5 | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 8.28 months |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 30 mg/m^2 | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 13.52 months |
| Mirvetuximab Soravtansine 5 mg/kg + PLD 40 mg/m^2 | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 32.94 months |
| Mirvetuximab Soravtansine 6 mg/kg + PLD 40 mg/m^2 | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 16.46 months |
| Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | NA months |
| Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 7.03 months |
| Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 7.23 months |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 5 mg/kg + Pembrolizumab 200 mg | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 2.53 months |
| Regimen D Dose Escalation: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 9.46 months |
| Regimen D Dose Expansion: Mirvetuximab Soravtansine 6 mg/kg + Pembrolizumab 200 mg | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 4.17 months |
| Regimen E: Mirvetuximab Soravtansine + Bevacizumab + Carboplatin | Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 | 13.50 months |