Tumors
Conditions
Keywords
FOLR-1 solid tumors
Brief summary
The purpose of this study is to test mirvetuximab soravtansine (IMGN853) in participants with ovarian cancer and other FOLR-1 positive tumors.
Detailed description
The study consists of a dose-escalation phase that will evaluate 2 dosing schedules (Schedule A and Schedule B) of mirvetuximab soravtansine and up to 5 dose-expansion groups at the maximum tolerated dose (MTD). The first 4 escalation cohorts will be single participant cohorts. Subsequent escalation cohorts will use a standard 3+3 design, with each cohort consisting of 3 or 4 to 6 participants. Data were collected and analysed for the escalation and expansion groups by dose schedule and not by individual dose.
Interventions
DRUGMirvetuximab soravtansine
Mirvetuximab soravtansine IV infusion will be administered as per dose and schedule specified in the respective arms.
Sponsors
ImmunoGen, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with advanced solid tumor that is refractory to standard treatment, for which no standard treatment is available, or the participant refuses standard therapy. * Participants must be willing to provide an archival tumor tissue block or slides for biomarker analysis. * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. * Time from prior therapy: 1. Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is shorter (6 weeks for prior nitrosoureas or mitomycin C). 2. Radiotherapy: wide-field radiotherapy (for example, greater than \[\>\] 30 percent \[%\] of marrow-bearing bones) completed at least four weeks, or focal radiation completed at least two weeks, prior to starting study drug. * Participants must have recovered or stabilized from all therapy-related toxicities. * Major surgery (not including placement of vascular access device or tumor biopsies) must be completed four weeks prior to Day 1. Participants must have recovered or stabilized from the side effects prior to study treatment. * Participants must have adequate hematologic, liver and kidney function. * Participants with central nervous system (CNS) disease involvement are eligible if they have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 and they meet all of the following criteria: Residual neurological symptoms less than or equal to (\<=) Grade 1; No dexamethasone requirement; and Follow-up magnetic resonance imaging (MRI) shows no progression of treated lesions and no new lesions appearing. * Participants must be willing and able to sign the informed consent form, and to adhere to the study visit schedule and other protocol requirements. * Women of childbearing potential and men must agree to use effective contraceptive methods while on study and for at least twelve weeks after the last dose of study drug. * Women of childbearing potential must have a negative pregnancy test prior to the first dose of study treatment.
Exclusion criteria
* Grade \>1 neuropathy. * Any active or chronic corneal disorder, including, but not limited to the following: Sjogren's syndrome, Fuch's corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring ongoing treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, acquired monocular vision. * Serious concurrent illness, including, but not limited to the following: 1. Clinically relevant active infection including known active hepatitis B or C, Human Immunodeficiency Virus (HIV) infection, varicella-zoster virus (shingles) or cytomegalovirus infection or any other known concurrent infectious disease, requiring IV antibiotics within 2 weeks of study enrollment. 2. Significant cardiac disease such as recent myocardial infarction (\<=6 months prior to Day 1), unstable angina pectoris, uncontrolled congestive heart failure (New York Heart Association \>class II), uncontrolled hypertension (greater than or equal to \[\>=\] Common Terminology Criteria for Adverse Events Version 4.03 \[CTCAE v4.03\] Grade 3), uncontrolled cardiac arrhythmias, severe aortic stenosis, or \>=Grade 3 cardiac toxicity following prior chemotherapy. 3. History of multiple sclerosis or other demyelinating disease, Eaton-Lambert syndrome (para-neoplastic syndrome), history of hemorrhagic or ischemic stroke within the last six months, or alcoholic liver disease. 4. Previous clinical diagnosis of treatment-related pneumonitis. * Any other concomitant anti-cancer treatment such as immunotherapy, biotherapy, radiotherapy, chemotherapy, investigative therapy, or high-dose steroids; however, low dose steroids and Luteinizing Hormone Releasing Hormone (LHRH) at doses that have been stable for \>=14 days are permitted for participants with prostate cancer. * Known hypersensitivity to previous monoclonal antibody therapy or maytansinoids. * Prior history of solid tumor malignancy within the last 3 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer (participants must have shown no evidence of active disease for 2 years prior to enrollment). * Concomitant administration of folate-containing vitamins. * Participants who have received prior allogeneic or autologous bone marrow transplants. * Women of childbearing potential who are pregnant or breast feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Escalation Phase: Maximum Tolerated Dose (MTD) of Mirvetuximab Soravtansine | Cycle 1 (21 days) | MTD was defined as the highest dose at which 1 or fewer among 6 participants or less than or equal to (\<=) 33 percent (%) experienced a dose-limiting toxicity (DLT) (calculated based on adjusted ideal body weight \[AIBW\]). AIBW was calculated as ideal body weight (IBW) + 0.4 \* (actual weight - IBW), where IBW for men was 0.9 \* height in centimeters (cm) - 88 and IBW for women was 0.9 \* height in cm - 92. DLT was defined as a treatment-emergent adverse event (TEAE) or abnormal laboratory value related to study treatment (that is, assessed as unrelated to disease, intercurrent illness, or concomitant medications), including those TEAEs and abnormal laboratory values that resulted in a failure to meet the criteria for re-treatment. |
| Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of Mirvetuximab Soravtansine | Cycle 1 (21 days) | RP2D was determined by MTD. MTD was defined as the highest dose at which 1 or fewer among 6 participants or \<=33% experienced a DLT. DLT was defined as a TEAE or abnormal laboratory value related to study treatment (that is, assessed as unrelated to disease, intercurrent illness, or concomitant medications), including those TEAEs and abnormal laboratory values that resulted in a failure to meet the criteria for re-treatment. Available clinical data indicated that the MTD defined for the Q3W schedule was equal to the RP2D. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | From first dose of study drug up to 28 days after last dose of study drug (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC) | Physical examination included assessments of general appearance, skin, head (eyes, ears, nose, and throat), neck, lungs, heart, abdomen, back, lymph nodes, extremities, and neurological system. Vital signs included assessment of blood pressure, pulse rate, respiratory rate and body temperature. |
| Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | Baseline up to end of treatment (EOT) (up to maximum 124 weeks) | Standard ECGs were performed in triplicate at 2- to 5-minute intervals during the study. A single ECG was performed at the end of treatment visit and as clinically indicated. |
| Number of Participants With Treatment-Emergent Ocular AEs | From first dose of study drug up to 28 days after last dose of study drug (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC) | Ocular AEs included keratopathy and blurred vision. An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to study drug. TEAEs were defined as any AE that emerged on or after the first dose, and within 28 days of the last dose. |
| Maximum Observed Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Cycle 1, 3: Day 1 (pre-infusion; within 10 minutes [min] of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion) | Pharmacokinetic (PK) parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3. |
| Cmax of Free DM4 and S-Methyl DM4 at RP2D | Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion) | PK parameters were calculated using standard non-compartmental methods. PK analysis of free N2'-\[4-\[(3-carboxypropyl)dithio\]-4-methyl-1-oxo-2-sulfopentyl\]-N2'-deacetylmaytansine (DM4) and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3. |
| Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion) | PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3. |
| AUC0-inf of Free DM4 and S-Methyl DM4 at RP2D | Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion) | PK parameters were calculated using standard non-compartmental methods. PK analysis of free DM4 and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3. |
| Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion) | PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3. |
| AUClast of Free DM4 and S-Methyl DM4 at RP2D | Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion) | PK parameters were calculated using standard non-compartmental methods. PK analysis of free DM4 and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3. |
| Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-Methyl DM4 at RP2D | Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion) | PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine, total M9346A antibody, DM4, and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3. |
| Number of Participants With TEAEs | From first dose of study drug up to 28 days after last dose of study drug (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC) | An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have 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 on following scale: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death. Serious AEs include 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 listed in this definition. TEAEs were defined as any AE that emerged on or after the first dose, and within 28 days of the last dose. |
| CL of DM4 and S-Methyl DM4 at RP2D | Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion) | PK parameters were calculated using standard non-compartmental methods. PK analysis of DM4 and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3. |
| Time to Reach Maximum Observed Concentration (Tmax) of Mirvetuximab Soravtansine, Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion) | PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine, free DM4, S-methyl DM4, and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3. |
| Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion) | PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine, free DM4, S-methyl DM4, and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3. |
| Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | From first dose of study drug until first BOR of CR or PR (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC) | ORR was defined as percentage of participants with a best overall response (BOR) of complete response (CR) or 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 (SoD) of target lesions, taking as reference the baseline SoD. |
| Duration of Response (DOR) as Assessed by RECIST v1.1 | From the date of first response (CR or PR) until the date of PD (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC) | DOR was defined as the time from the date of the first response (CR or PR), whichever was recorded first, until the date of progressive disease (PD). PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. DOR was only defined for participants who had a BOR of CR or PR using the method of Kaplan-Meier. |
| Progression-Free Survival (PFS) as Assessed by RECIST v1.1 | From first dose of study drug until PD or death whichever occurred first (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC) | PFS was defined as the time from initiation of study drug until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD 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 to Progression (TTP) as Assessed by RECIST v1.1 | From first dose of study drug until PD (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC) | TTP was defined as the time from initiation of study drug until PD, estimated using the method of Kaplan-Meier. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD 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. |
| Number of Participants With Anti-Drug Antibodies (ADA) | Baseline up to follow-up visit (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC) | During the conduct of the study, a single immunogenicity assay was developed to concurrently detect human antibodies against all components of mirvetuximab soravtansine, including the humanized anti-FOLR1 antibody, the cleavable disulfide linker, and the cytotoxic maytansinoid, DM4. Therefore, immunogenicity results were reported as ADA titers, and did not distinguish between human anti-drug or anti-human titers. |
| Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | From first dose of study drug until CA-125 response (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC) | CA-125 response was defined as at least 50% reduction in CA-125 levels from baseline. The date of response corresponded to the date when the CA 125 level was first reduced by 50%. |
| Clearance (CL) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion) | PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3. |
| Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | From first dose of study drug up to 28 days after last dose of study drug (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC) | Laboratory parameters included serum chemistry (alanine aminotransferase \[ALT\]/serum glutamic pyruvic transaminase \[SGPT\], aspartate aminotransferase \[AST\]/serum glutamic oxaloacetic transaminase \[SGOT\], albumin, alkaline phosphatase, bilirubin, calcium, creatinine, glucose, magnesium, phosphorous, potassium, sodium), hematology (hemoglobin, lymphocytes, neutrophils, platelets, white blood cells) and coagulation (international normalized ratio \[INR\], partial thromboplastin time \[PTT\]). Clinically significant laboratory values were defined as per NCI CTCAE v.03 Grade 3 or higher. A grading (severity) scale was provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Only participants who shifted from a baseline value of Grade \<=2 to a post-baseline Grade 3/4 on-treatment, are reported. |
Countries
Canada, United States
Participant flow
Recruitment details
A total of 206 participants were enrolled in this study, of whom 69 participants (44 to receive Schedule A and 25 to receive Schedule B treatment) were entered in dose-escalation phase and 137 participants (113 with epithelial ovarian cancer \[EOC\] and 24 with endometrial cancer \[EC\]) were entered in dose-expansion phase. Doses calculated initially based on participant's total body weight (TBW); then from protocol amendment 5 onwards, calculated based on adjusted ideal body weight (AIBW).
Pre-assignment details
Dose expansion Cohort 4 was planned to enroll relapsed/refractory non-small cell lung cancer (NSCLC) adenocarcinoma or bronchoalveolar carcinoma (BAC) but no participants were enrolled due to a company decision to focus on endometrial and ovarian carcinoma for the initial investigation.
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 0.15 mg/kg Q3W) Participants received mirvetuximab soravtansine 0.15 mg/kg IV infusion on Day 1 of every 21-day (Q3W) cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 2 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 0.5 mg/kg Q3W) Participants received mirvetuximab soravtansine 0.5 mg/kg IV infusion on Day 1 of every 21-day (Q3W) cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 1 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) Participants received mirvetuximab soravtansine 1.0 mg/kg IV infusion on Day 1 of every 21-day (Q3W) cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 1 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) Participants received mirvetuximab soravtansine 2.0 mg/kg IV infusion on Day 1 of every 21-day (Q3W) cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 1 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) Participants received mirvetuximab soravtansine 3.3 mg/kg IV infusion on Day 1 of every 21-day (Q3W) cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 9 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) Participants received mirvetuximab soravtansine 5.0 mg/kg IV infusion on Day 1 of every 21-day (Q3W) cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 18 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) Participants received mirvetuximab soravtansine 6.0 mg/kg IV infusion on Day 1 of every 21-day (Q3W) cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 7 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) Participants received mirvetuximab soravtansine 7.0 mg/kg IV infusion on Day 1 of every 21-day (Q3W) cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 5 |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) Participants received mirvetuximab soravtansine 1.1 mg/kg IV infusion on Days 1, 8, and 15 of every 28-day cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 5 |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) Participants received mirvetuximab soravtansine 1.8 mg/kg IV infusion on Days 1, 8, and 15 of every 28-day cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 4 |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) Participants received mirvetuximab soravtansine 2.0 mg/kg IV infusion on Days 1, 8, and 15 of every 28-day cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 9 |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) Participants received mirvetuximab soravtansine 2.5 mg/kg IV infusion on Days 1, 8, and 15 of every 28-day cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 7 |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) Participants with EOC, primary peritoneal cancer, or fallopian tube cancer resistant to platinum-based therapy received mirvetuximab soravtansine 6.0 mg/kg (MTD) IV infusion on Day 1 of every 21-day (Q3W) cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 46 |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) Participants with FOLR1-positive uterine cancer (that was advanced or recurrent and had received at least 1 platinum-based regimen, and no more than 5 prior systemic treatment regimens for EC) received mirvetuximab soravtansine 6.0 mg/kg (MTD) IV infusion on Day 1 of every 21-day (Q3W) cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 24 |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) Participants with biopsy-accessible relapsed or refractory ovarian cancer, primary peritoneal cancer, or fallopian tube cancer received mirvetuximab soravtansine 6.0 mg/kg (MTD) IV infusion on Day 1 of every 21-day (Q3W) cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 27 |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) Participants with EOC primary peritoneal cancer or fallopian tube cancer (that had relapsed following platinum-based therapy, excluding those participants with primary platinum refractory disease or low grade or clear cell ovarian cancer) received mirvetuximab soravtansine 6.0 mg/kg (MTD) IV infusion on Day 1 of every 21-day (Q3W) cycle. Participants continued to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever came first, or until the sponsor terminated the study. | 40 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose Escalation: Maximum 101.3 Weeks | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Dose Escalation: Maximum 101.3 Weeks | Began New Anticancer Therapy | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Dose Escalation: Maximum 101.3 Weeks | Clinical Progression | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 1 | 1 | 2 | 0 | 0 | 0 | 0 |
| Dose Escalation: Maximum 101.3 Weeks | Death | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation: Maximum 101.3 Weeks | Disease Progression | 0 | 1 | 1 | 1 | 8 | 13 | 5 | 4 | 3 | 3 | 6 | 3 | 0 | 0 | 0 | 0 |
| Dose Escalation: Maximum 101.3 Weeks | Investigator Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation: Maximum 101.3 Weeks | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Expansion: Maximum 124 Weeks | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 2 | 2 | 2 |
| Dose Expansion: Maximum 124 Weeks | Began New Anticancer Therapy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Dose Expansion: Maximum 124 Weeks | Clinical Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 | 3 | 2 |
| Dose Expansion: Maximum 124 Weeks | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 2 | 0 | 3 |
| Dose Expansion: Maximum 124 Weeks | Disease Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 32 | 13 | 20 | 27 |
| Dose Expansion: Maximum 124 Weeks | Investigator Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Dose Expansion: Maximum 124 Weeks | Other Than Specified | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Dose Expansion: Maximum 124 Weeks | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 4 | 2 | 5 |
Baseline characteristics
| Characteristic | Total | Dose Escalation: Schedule A (Mirvetuximab Soravtansine 0.5 mg/kg Q3W) | Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Dose Escalation: Schedule A (Mirvetuximab Soravtansine 0.15 mg/kg Q3W) | Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 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 | 0 Participants |
| Age, Categorical >=65 years | 84 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 7 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 21 Participants | 14 Participants | 10 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 122 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 6 Participants | 11 Participants | 4 Participants | 3 Participants | 2 Participants | 2 Participants | 5 Participants | 5 Participants | 25 Participants | 10 Participants | 17 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 189 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 9 Participants | 16 Participants | 7 Participants | 3 Participants | 4 Participants | 4 Participants | 9 Participants | 6 Participants | 44 Participants | 23 Participants | 26 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 13 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 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 | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 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 | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 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 | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 187 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 7 Participants | 18 Participants | 6 Participants | 5 Participants | 5 Participants | 4 Participants | 9 Participants | 5 Participants | 41 Participants | 23 Participants | 25 Participants | 34 Participants |
| Sex: Female, Male Female | 200 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 9 Participants | 16 Participants | 5 Participants | 4 Participants | 4 Participants | 4 Participants | 9 Participants | 7 Participants | 46 Participants | 24 Participants | 27 Participants | 40 Participants |
| Sex: Female, Male Male | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 1 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 | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 2 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 9 | 1 / 18 | 0 / 7 | 0 / 5 | 0 / 5 | 0 / 4 | 1 / 9 | 0 / 7 | 4 / 46 | 4 / 24 | 1 / 27 | 4 / 40 |
| other Total, other adverse events | 2 / 2 | 0 / 1 | 1 / 1 | 1 / 1 | 9 / 9 | 18 / 18 | 7 / 7 | 5 / 5 | 5 / 5 | 4 / 4 | 9 / 9 | 7 / 7 | 45 / 46 | 24 / 24 | 27 / 27 | 40 / 40 |
| serious Total, serious adverse events | 2 / 2 | 0 / 1 | 1 / 1 | 0 / 1 | 0 / 9 | 5 / 18 | 1 / 7 | 2 / 5 | 2 / 5 | 3 / 4 | 4 / 9 | 4 / 7 | 18 / 46 | 11 / 24 | 9 / 27 | 17 / 40 |
Outcome results
Primary
Dose-Escalation Phase: Maximum Tolerated Dose (MTD) of Mirvetuximab Soravtansine
MTD was defined as the highest dose at which 1 or fewer among 6 participants or less than or equal to (\<=) 33 percent (%) experienced a dose-limiting toxicity (DLT) (calculated based on adjusted ideal body weight \[AIBW\]). AIBW was calculated as ideal body weight (IBW) + 0.4 \* (actual weight - IBW), where IBW for men was 0.9 \* height in centimeters (cm) - 88 and IBW for women was 0.9 \* height in cm - 92. DLT was defined as a treatment-emergent adverse event (TEAE) or abnormal laboratory value related to study treatment (that is, assessed as unrelated to disease, intercurrent illness, or concomitant medications), including those TEAEs and abnormal laboratory values that resulted in a failure to meet the criteria for re-treatment.
Time frame: Cycle 1 (21 days)
Population: Safety population included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Dose-Escalation Phase: Maximum Tolerated Dose (MTD) of Mirvetuximab Soravtansine | 6.0 mg/kg |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Dose-Escalation Phase: Maximum Tolerated Dose (MTD) of Mirvetuximab Soravtansine | 2.0 mg/kg |
Primary
Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of Mirvetuximab Soravtansine
RP2D was determined by MTD. MTD was defined as the highest dose at which 1 or fewer among 6 participants or \<=33% experienced a DLT. DLT was defined as a TEAE or abnormal laboratory value related to study treatment (that is, assessed as unrelated to disease, intercurrent illness, or concomitant medications), including those TEAEs and abnormal laboratory values that resulted in a failure to meet the criteria for re-treatment. Available clinical data indicated that the MTD defined for the Q3W schedule was equal to the RP2D.
Time frame: Cycle 1 (21 days)
Population: Safety population included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of Mirvetuximab Soravtansine | 6.0 mg/kg |
Secondary
Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D
PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Time frame: Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Population: PK Population included all participants who received at least 1 infusion of mirvetuximab soravtansine and had evaluable PK data. 'Overall number of participants analyzed' = participants who received mirvetuximab soravtansine at 6 mg/kg AIBW. 'Number analyzed' = participants evaluable for this outcome for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Mirvetuximab soravtansine at Cycle 1 | 17.39 hours*milligrams/milliliter (hr*mg/mL) | Standard Deviation 4.341 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Mirvetuximab soravtansine at Cycle 3 | 20.40 hours*milligrams/milliliter (hr*mg/mL) | Standard Deviation 5.144 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Total M9346A antibody at Cycle 1 | 24.00 hours*milligrams/milliliter (hr*mg/mL) | Standard Deviation 7.316 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Total M9346A antibody at Cycle 3 | 37.27 hours*milligrams/milliliter (hr*mg/mL) | Standard Deviation 12.54 |
Secondary
Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D
PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Time frame: Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Population: PK Population included all participants who received at least 1 infusion of mirvetuximab soravtansine and had evaluable PK data. 'Overall number of participants analyzed' = participants who received mirvetuximab soravtansine at 6 mg/kg AIBW. 'Number analyzed' = participants evaluable for this outcome for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Total M9346A antibody at Cycle 3 | 29.29 hr*mg/mL | Standard Deviation 9.613 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Mirvetuximab soravtansine at Cycle 1 | 16.44 hr*mg/mL | Standard Deviation 4.177 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Mirvetuximab soravtansine at Cycle 3 | 18.91 hr*mg/mL | Standard Deviation 4.94 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Total M9346A antibody at Cycle 1 | 20.27 hr*mg/mL | Standard Deviation 5.903 |
Secondary
AUC0-inf of Free DM4 and S-Methyl DM4 at RP2D
PK parameters were calculated using standard non-compartmental methods. PK analysis of free DM4 and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Time frame: Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Population: PK Population included all participants who received at least 1 infusion of mirvetuximab soravtansine and had evaluable PK data. 'Overall number of participants analyzed' = participants who received mirvetuximab soravtansine at 6 mg/kg AIBW. 'Number analyzed' = participants evaluable for this outcome for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | AUC0-inf of Free DM4 and S-Methyl DM4 at RP2D | DM4 at Cycle 1 | 292.9 hours*nanograms/milliliter (hr*ng/mL) | Standard Deviation 129.2 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | AUC0-inf of Free DM4 and S-Methyl DM4 at RP2D | DM4 at Cycle 3 | 290.6 hours*nanograms/milliliter (hr*ng/mL) | Standard Deviation 98.52 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | AUC0-inf of Free DM4 and S-Methyl DM4 at RP2D | S-methyl DM4 at Cycle 1 | 2656 hours*nanograms/milliliter (hr*ng/mL) | Standard Deviation 2722 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | AUC0-inf of Free DM4 and S-Methyl DM4 at RP2D | S-methyl DM4 at Cycle 3 | 1928 hours*nanograms/milliliter (hr*ng/mL) | Standard Deviation 1108 |
Secondary
AUClast of Free DM4 and S-Methyl DM4 at RP2D
PK parameters were calculated using standard non-compartmental methods. PK analysis of free DM4 and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Time frame: Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Population: PK Population included all participants who received at least 1 infusion of mirvetuximab soravtansine and had evaluable PK data. 'Overall number of participants analyzed' = participants who received mirvetuximab soravtansine at 6 mg/kg AIBW. 'Number analyzed' = participants evaluable for this outcome for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | AUClast of Free DM4 and S-Methyl DM4 at RP2D | DM4 at Cycle 1 | 246.0 hr*ng/mL | Standard Deviation 133.3 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | AUClast of Free DM4 and S-Methyl DM4 at RP2D | DM4 at Cycle 3 | 270.1 hr*ng/mL | Standard Deviation 95.62 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | AUClast of Free DM4 and S-Methyl DM4 at RP2D | S-methyl DM4 at Cycle 1 | 2485 hr*ng/mL | Standard Deviation 2536 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | AUClast of Free DM4 and S-Methyl DM4 at RP2D | S-methyl DM4 at Cycle 3 | 1806 hr*ng/mL | Standard Deviation 1046 |
Secondary
Clearance (CL) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D
PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Time frame: Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Population: PK Population included all participants who received at least 1 infusion of mirvetuximab soravtansine and had evaluable PK data. 'Overall number of participants analyzed' = participants who received mirvetuximab soravtansine at 6 mg/kg AIBW. 'Number analyzed' = participants evaluable for this outcome for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Clearance (CL) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Mirvetuximab soravtansine at Cycle 1 | 22.20 milliliters per hour (mL/hr) | Standard Deviation 6.476 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Clearance (CL) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Mirvetuximab soravtansine at Cycle 3 | 19.80 milliliters per hour (mL/hr) | Standard Deviation 4.953 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Clearance (CL) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Total M9346A antibody at Cycle 1 | 16.89 milliliters per hour (mL/hr) | Standard Deviation 7.155 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Clearance (CL) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Total M9346A antibody at Cycle 3 | 13.26 milliliters per hour (mL/hr) | Standard Deviation 4.956 |
Secondary
CL of DM4 and S-Methyl DM4 at RP2D
PK parameters were calculated using standard non-compartmental methods. PK analysis of DM4 and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Time frame: Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Population: PK Population included all participants who received at least 1 infusion of mirvetuximab soravtansine and had evaluable PK data. 'Overall number of participants analyzed' = participants who received mirvetuximab soravtansine at 6 mg/kg AIBW. 'Number analyzed' = participants evaluable for this outcome for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | CL of DM4 and S-Methyl DM4 at RP2D | DM4 at Cycle 1 | 1421 Liters per hour (L/hr) | Standard Deviation 560.2 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | CL of DM4 and S-Methyl DM4 at RP2D | DM4 at Cycle 3 | 1338 Liters per hour (L/hr) | Standard Deviation 438.8 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | CL of DM4 and S-Methyl DM4 at RP2D | S-methyl DM4 at Cycle 1 | 218.9 Liters per hour (L/hr) | Standard Deviation 128.5 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | CL of DM4 and S-Methyl DM4 at RP2D | S-methyl DM4 at Cycle 3 | 258.4 Liters per hour (L/hr) | Standard Deviation 173.8 |
Secondary
Cmax of Free DM4 and S-Methyl DM4 at RP2D
PK parameters were calculated using standard non-compartmental methods. PK analysis of free N2'-\[4-\[(3-carboxypropyl)dithio\]-4-methyl-1-oxo-2-sulfopentyl\]-N2'-deacetylmaytansine (DM4) and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Time frame: Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Population: PK Population included all participants who received at least 1 infusion of mirvetuximab soravtansine and had evaluable PK data. 'Overall number of participants analyzed' = participants who received mirvetuximab soravtansine at 6 mg/kg AIBW. 'Number analyzed' = participants evaluable for this outcome for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Cmax of Free DM4 and S-Methyl DM4 at RP2D | DM4 at Cycle 1 | 5.014 nanograms per milliliter (ng/mL) | Standard Deviation 3.119 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Cmax of Free DM4 and S-Methyl DM4 at RP2D | DM4 at Cycle 3 | 5.016 nanograms per milliliter (ng/mL) | Standard Deviation 2.389 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Cmax of Free DM4 and S-Methyl DM4 at RP2D | S-methyl DM4 at Cycle 1 | 12.43 nanograms per milliliter (ng/mL) | Standard Deviation 12.39 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Cmax of Free DM4 and S-Methyl DM4 at RP2D | S-methyl DM4 at Cycle 3 | 9.974 nanograms per milliliter (ng/mL) | Standard Deviation 5.485 |
Secondary
Duration of Response (DOR) as Assessed by RECIST v1.1
DOR was defined as the time from the date of the first response (CR or PR), whichever was recorded first, until the date of progressive disease (PD). PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. DOR was only defined for participants who had a BOR of CR or PR using the method of Kaplan-Meier.
Time frame: From the date of first response (CR or PR) until the date of PD (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Population: Efficacy-evaluable population included participants who had radiographic assessment at baseline, received at least 1 dose of study drug, and had at least 1 post-dose tumor assessment or died or clinically progressed within 105 days of last dose. 'Overall number of participants analyzed'=participants who had a BOR of CR or PR. Data by group only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Duration of Response (DOR) as Assessed by RECIST v1.1 | 21.3 weeks |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Duration of Response (DOR) as Assessed by RECIST v1.1 | 60.2 weeks |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Duration of Response (DOR) as Assessed by RECIST v1.1 | 19.3 weeks |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Duration of Response (DOR) as Assessed by RECIST v1.1 | 28.6 weeks |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D
Pharmacokinetic (PK) parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Time frame: Cycle 1, 3: Day 1 (pre-infusion; within 10 minutes [min] of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Population: PK Population included all participants who received at least 1 infusion of mirvetuximab soravtansine and had evaluable PK data. 'Overall number of participants analyzed' = participants who received mirvetuximab soravtansine at 6 mg/kg AIBW. 'Number analyzed' = participants evaluable for this outcome for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Maximum Observed Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Mirvetuximab soravtansine at Cycle 1 | 146.9 micrograms per milliliter (mcg/mL) | Standard Deviation 30.14 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Maximum Observed Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Mirvetuximab soravtansine at Cycle 3 | 154.6 micrograms per milliliter (mcg/mL) | Standard Deviation 33.08 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Maximum Observed Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Total M9346A antibody at Cycle 1 | 149.2 micrograms per milliliter (mcg/mL) | Standard Deviation 33.74 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Maximum Observed Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D | Total M9346A antibody at Cycle 3 | 170.4 micrograms per milliliter (mcg/mL) | Standard Deviation 40.55 |
Secondary
Number of Participants With Anti-Drug Antibodies (ADA)
During the conduct of the study, a single immunogenicity assay was developed to concurrently detect human antibodies against all components of mirvetuximab soravtansine, including the humanized anti-FOLR1 antibody, the cleavable disulfide linker, and the cytotoxic maytansinoid, DM4. Therefore, immunogenicity results were reported as ADA titers, and did not distinguish between human anti-drug or anti-human titers.
Time frame: Baseline up to follow-up visit (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Population: Immunogenicity population included all participants who received at least 1 infusion of mirvetuximab soravtansine and had evaluable immunogenicity data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Number of Participants With Anti-Drug Antibodies (ADA) | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Number of Participants With Anti-Drug Antibodies (ADA) | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Number of Participants With Anti-Drug Antibodies (ADA) | 1 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Number of Participants With Anti-Drug Antibodies (ADA) | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Number of Participants With Anti-Drug Antibodies (ADA) | 1 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Number of Participants With Anti-Drug Antibodies (ADA) | 1 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Number of Participants With Anti-Drug Antibodies (ADA) | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Number of Participants With Anti-Drug Antibodies (ADA) | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Number of Participants With Anti-Drug Antibodies (ADA) | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Number of Participants With Anti-Drug Antibodies (ADA) | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Number of Participants With Anti-Drug Antibodies (ADA) | 1 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Number of Participants With Anti-Drug Antibodies (ADA) | 0 Participants |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Anti-Drug Antibodies (ADA) | 0 Participants |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Anti-Drug Antibodies (ADA) | 7 Participants |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Anti-Drug Antibodies (ADA) | 2 Participants |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Anti-Drug Antibodies (ADA) | 2 Participants |
Secondary
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)
Standard ECGs were performed in triplicate at 2- to 5-minute intervals during the study. A single ECG was performed at the end of treatment visit and as clinically indicated.
Time frame: Baseline up to end of treatment (EOT) (up to maximum 124 weeks)
Population: Safety population included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 3 Participants |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 2 Participants |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 1 Participants |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 1 Participants |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs
Physical examination included assessments of general appearance, skin, head (eyes, ears, nose, and throat), neck, lungs, heart, abdomen, back, lymph nodes, extremities, and neurological system. Vital signs included assessment of blood pressure, pulse rate, respiratory rate and body temperature.
Time frame: From first dose of study drug up to 28 days after last dose of study drug (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Population: Safety population included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs | 0 Participants |
Secondary
Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses
CA-125 response was defined as at least 50% reduction in CA-125 levels from baseline. The date of response corresponded to the date when the CA 125 level was first reduced by 50%.
Time frame: From first dose of study drug until CA-125 response (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Population: CA-125 evaluable population included participants who had a baseline CA-125 value greater than or equal to (\>=) 2 \* upper limit of normal (ULN), received at least 1 dose of study drug, and had at least 1 post-dose CA-125 assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 3 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 1 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 1 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 1 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 2 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 2 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 3 Participants |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 23 Participants |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 4 Participants |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 11 Participants |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses | 17 Participants |
Secondary
Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study
Laboratory parameters included serum chemistry (alanine aminotransferase \[ALT\]/serum glutamic pyruvic transaminase \[SGPT\], aspartate aminotransferase \[AST\]/serum glutamic oxaloacetic transaminase \[SGOT\], albumin, alkaline phosphatase, bilirubin, calcium, creatinine, glucose, magnesium, phosphorous, potassium, sodium), hematology (hemoglobin, lymphocytes, neutrophils, platelets, white blood cells) and coagulation (international normalized ratio \[INR\], partial thromboplastin time \[PTT\]). Clinically significant laboratory values were defined as per NCI CTCAE v.03 Grade 3 or higher. A grading (severity) scale was provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Only participants who shifted from a baseline value of Grade \<=2 to a post-baseline Grade 3/4 on-treatment, are reported.
Time frame: From first dose of study drug up to 28 days after last dose of study drug (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Population: Safety population included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 1 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 1 Participants |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 1 Participants |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 1 Participants |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 1 Participants |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | PTT: Grade 2 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 0 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Lymphocytes: Grade 2 to Grade 3 | 1 Participants |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Magnesium: Grade 2 to Grade 3 | 0 Participants |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study | Glucose: Grade 0 to Grade 3 | 0 Participants |
Secondary
Number of Participants With TEAEs
An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have 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 on following scale: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death. Serious AEs include 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 listed in this definition. TEAEs were defined as any AE that emerged on or after the first dose, and within 28 days of the last dose.
Time frame: From first dose of study drug up to 28 days after last dose of study drug (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Population: Safety population included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | Any TEAE | 2 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | Grade >=3 TEAEs | 2 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | SAEs | 2 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Number of Participants With TEAEs | SAEs | 1 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Number of Participants With TEAEs | Any TEAE | 1 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Number of Participants With TEAEs | Grade >=3 TEAEs | 1 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Number of Participants With TEAEs | Grade >=3 TEAEs | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Number of Participants With TEAEs | Any TEAE | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Number of Participants With TEAEs | SAEs | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Number of Participants With TEAEs | SAEs | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Number of Participants With TEAEs | Any TEAE | 1 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Number of Participants With TEAEs | Grade >=3 TEAEs | 1 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Number of Participants With TEAEs | SAEs | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Number of Participants With TEAEs | Any TEAE | 9 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Number of Participants With TEAEs | Grade >=3 TEAEs | 1 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Number of Participants With TEAEs | SAEs | 5 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Number of Participants With TEAEs | Any TEAE | 18 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Number of Participants With TEAEs | Grade >=3 TEAEs | 8 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Number of Participants With TEAEs | SAEs | 1 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Number of Participants With TEAEs | Grade >=3 TEAEs | 1 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Number of Participants With TEAEs | Any TEAE | 7 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Number of Participants With TEAEs | SAEs | 2 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Number of Participants With TEAEs | Any TEAE | 5 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Number of Participants With TEAEs | Grade >=3 TEAEs | 3 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Number of Participants With TEAEs | SAEs | 2 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Number of Participants With TEAEs | Grade >=3 TEAEs | 2 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Number of Participants With TEAEs | Any TEAE | 5 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Number of Participants With TEAEs | Any TEAE | 4 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Number of Participants With TEAEs | SAEs | 3 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Number of Participants With TEAEs | Grade >=3 TEAEs | 3 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Number of Participants With TEAEs | Grade >=3 TEAEs | 4 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Number of Participants With TEAEs | SAEs | 4 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Number of Participants With TEAEs | Any TEAE | 9 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Number of Participants With TEAEs | SAEs | 4 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Number of Participants With TEAEs | Any TEAE | 7 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Number of Participants With TEAEs | Grade >=3 TEAEs | 4 Participants |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | Grade >=3 TEAEs | 24 Participants |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | Any TEAE | 46 Participants |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | SAEs | 18 Participants |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | Grade >=3 TEAEs | 12 Participants |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | SAEs | 11 Participants |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | Any TEAE | 24 Participants |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | Any TEAE | 27 Participants |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | SAEs | 9 Participants |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | Grade >=3 TEAEs | 14 Participants |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | SAEs | 17 Participants |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | Any TEAE | 40 Participants |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) | Number of Participants With TEAEs | Grade >=3 TEAEs | 24 Participants |
Secondary
Number of Participants With Treatment-Emergent Ocular AEs
Ocular AEs included keratopathy and blurred vision. An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to study drug. TEAEs were defined as any AE that emerged on or after the first dose, and within 28 days of the last dose.
Time frame: From first dose of study drug up to 28 days after last dose of study drug (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Population: Safety population included all participants who were enrolled and received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Number of Participants With Treatment-Emergent Ocular AEs | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Number of Participants With Treatment-Emergent Ocular AEs | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Number of Participants With Treatment-Emergent Ocular AEs | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Number of Participants With Treatment-Emergent Ocular AEs | 0 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 3.3 mg/kg Q3W) | Number of Participants With Treatment-Emergent Ocular AEs | 1 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 5.0 mg/kg Q3W) | Number of Participants With Treatment-Emergent Ocular AEs | 4 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 6.0 mg/kg Q3W) | Number of Participants With Treatment-Emergent Ocular AEs | 2 Participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 7.0 mg/kg Q3W) | Number of Participants With Treatment-Emergent Ocular AEs | 5 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.1 mg/kg Weekly) | Number of Participants With Treatment-Emergent Ocular AEs | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 1.8 mg/kg Weekly) | Number of Participants With Treatment-Emergent Ocular AEs | 3 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.0 mg/kg Weekly) | Number of Participants With Treatment-Emergent Ocular AEs | 0 Participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine 2.5 mg/kg Weekly) | Number of Participants With Treatment-Emergent Ocular AEs | 2 Participants |
| Dose Expansion: Cohort 1 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Treatment-Emergent Ocular AEs | 24 Participants |
| Dose Expansion: Cohort 2 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Treatment-Emergent Ocular AEs | 9 Participants |
| Dose Expansion: Cohort 3 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Treatment-Emergent Ocular AEs | 14 Participants |
| Dose Expansion: Cohort 5 (Mirvetuximab Soravtansine Q3W) | Number of Participants With Treatment-Emergent Ocular AEs | 18 Participants |
Secondary
Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
ORR was defined as percentage of participants with a best overall response (BOR) of complete response (CR) or 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 (SoD) of target lesions, taking as reference the baseline SoD.
Time frame: From first dose of study drug until first BOR of CR or PR (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Population: Efficacy-evaluable population included participants who had radiographic assessment at baseline, received at least 1 dose of study drug, and had at least 1 post-dose tumor assessment or died or clinically progressed within 105 days of last dose. Data was only collected and reported combined for dose-escalation phase and not by individual doses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 5 percentage of participants |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 13 percentage of participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 30 percentage of participants |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 8 percentage of participants |
Secondary
Progression-Free Survival (PFS) as Assessed by RECIST v1.1
PFS was defined as the time from initiation of study drug until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD 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 PD or death whichever occurred first (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Population: Efficacy-evaluable population included participants who had radiographic assessment at baseline, received at least 1 dose of study drug, and had at least 1 post-dose tumor assessment or died or clinically progressed within 105 days of last dose. Data was only collected and reported combined for dose-escalation phase and not by individual doses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Progression-Free Survival (PFS) as Assessed by RECIST v1.1 | 2.6 months |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Progression-Free Survival (PFS) as Assessed by RECIST v1.1 | 3.9 months |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Progression-Free Survival (PFS) as Assessed by RECIST v1.1 | 4.3 months |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Progression-Free Survival (PFS) as Assessed by RECIST v1.1 | 2.8 months |
Secondary
Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-Methyl DM4 at RP2D
PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine, total M9346A antibody, DM4, and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Time frame: Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Population: PK Population included all participants who received at least 1 infusion of mirvetuximab soravtansine and had evaluable PK data. 'Overall number of participants analyzed' = participants who received mirvetuximab soravtansine at 6 mg/kg AIBW. 'Number analyzed' = participants evaluable for this outcome for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-Methyl DM4 at RP2D | Mirvetuximab soravtansine at Cycle 1 | 119.4 hours | Standard Deviation 22.58 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-Methyl DM4 at RP2D | Mirvetuximab soravtansine at Cycle 3 | 127.8 hours | Standard Deviation 34.11 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-Methyl DM4 at RP2D | Total M9346A antibody at Cycle 1 | 186.7 hours | Standard Deviation 54.04 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-Methyl DM4 at RP2D | Total M9346A antibody at Cycle 3 | 218.8 hours | Standard Deviation 71.46 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-Methyl DM4 at RP2D | DM4 at Cycle 1 | 73.80 hours | Standard Deviation 28.99 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-Methyl DM4 at RP2D | DM4 at Cycle 3 | 80.62 hours | Standard Deviation 26.12 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-Methyl DM4 at RP2D | S-methyl DM4 at Cycle 1 | 122.2 hours | Standard Deviation 25.23 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-Methyl DM4 at RP2D | S-methyl DM4 at Cycle 3 | 130.4 hours | Standard Deviation 23.47 |
Secondary
Time to Progression (TTP) as Assessed by RECIST v1.1
TTP was defined as the time from initiation of study drug until PD, estimated using the method of Kaplan-Meier. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD 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 PD (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Population: Efficacy-evaluable population included participants who had radiographic assessment at baseline, received at least 1 dose of study drug, and had at least 1 post-dose tumor assessment or died or clinically progressed within 105 days of last dose. Data was only collected and reported combined for dose-escalation phase and not by individual doses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Time to Progression (TTP) as Assessed by RECIST v1.1 | 2.7 months |
| Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly) | Time to Progression (TTP) as Assessed by RECIST v1.1 | 3.9 months |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 1.0 mg/kg Q3W) | Time to Progression (TTP) as Assessed by RECIST v1.1 | 4.4 months |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine 2.0 mg/kg Q3W) | Time to Progression (TTP) as Assessed by RECIST v1.1 | 2.8 months |
Secondary
Time to Reach Maximum Observed Concentration (Tmax) of Mirvetuximab Soravtansine, Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D
PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine, free DM4, S-methyl DM4, and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Time frame: Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Population: PK Population included all participants who received at least 1 infusion of mirvetuximab soravtansine and had evaluable PK data. 'Overall number of participants analyzed' = participants who received mirvetuximab soravtansine at 6 mg/kg AIBW. 'Number analyzed' = participants evaluable for this outcome for specified categories.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Time to Reach Maximum Observed Concentration (Tmax) of Mirvetuximab Soravtansine, Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | Mirvetuximab soravtansine at Cycle 1 | 3.80 hours |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Time to Reach Maximum Observed Concentration (Tmax) of Mirvetuximab Soravtansine, Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | Mirvetuximab soravtansine at Cycle 3 | 3.20 hours |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Time to Reach Maximum Observed Concentration (Tmax) of Mirvetuximab Soravtansine, Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | Total M9346A antibody at Cycle 1 | 3.60 hours |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Time to Reach Maximum Observed Concentration (Tmax) of Mirvetuximab Soravtansine, Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | Total M9346A antibody at Cycle 3 | 3.20 hours |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Time to Reach Maximum Observed Concentration (Tmax) of Mirvetuximab Soravtansine, Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | DM4 at Cycle 1 | 5.80 hours |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Time to Reach Maximum Observed Concentration (Tmax) of Mirvetuximab Soravtansine, Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | DM4 at Cycle 3 | 5.00 hours |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Time to Reach Maximum Observed Concentration (Tmax) of Mirvetuximab Soravtansine, Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | S-methyl DM4 at Cycle 1 | 49.0 hours |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Time to Reach Maximum Observed Concentration (Tmax) of Mirvetuximab Soravtansine, Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | S-methyl DM4 at Cycle 3 | 23.0 hours |
Secondary
Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D
PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine, free DM4, S-methyl DM4, and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Time frame: Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Population: PK Population included all participants who received at least 1 infusion of mirvetuximab soravtansine and had evaluable PK data. 'Overall number of participants analyzed' = participants who received mirvetuximab soravtansine at 6 mg/kg AIBW. 'Number analyzed' = participants evaluable for this outcome for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | Mirvetuximab soravtansine at Cycle 3 | 3.172 Liters | Standard Deviation 1.022 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | Mirvetuximab soravtansine at Cycle 1 | 3.198 Liters | Standard Deviation 0.7422 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | Total M9346A antibody at Cycle 1 | 3.744 Liters | Standard Deviation 0.9183 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | Total M9346A antibody at Cycle 3 | 3.671 Liters | Standard Deviation 1.185 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | DM4 at Cycle 1 | 107400 Liters | Standard Deviation 38770 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | DM4 at Cycle 3 | 114300 Liters | Standard Deviation 48740 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | S-methyl DM4 at Cycle 1 | 41590 Liters | Standard Deviation 27890 |
| Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W) | Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D | S-methyl DM4 at Cycle 3 | 47520 Liters | Standard Deviation 40440 |