Epithelial Ovarian Cancer, Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Carcinoma
Conditions
Keywords
Epithelial ovarian cancer, Fallopian tube cancer, Primary peritoneal cancer, IMGN853, ADC, Antibody drug conjugate, ImmunoGen, Antibody, Folate receptor alpha, mirvetuximab soravtansine, Phase 3, platinum-resistant, MIRV
Brief summary
This is a Phase 3, open label, randomized study designed to compare the safety and efficacy of mirvetuximab soravtansine to that of selected single-agent chemotherapy (Investigator's choice) in women with platinum-resistant FR-alpha positive advanced EOC, primary peritoneal cancer and/or fallopian tube cancer.
Detailed description
Participants will be randomized to either mirvetuximab soravtansine or investigator's choice chemotherapy.
Interventions
DRUGMirvetuximab soravtansine
Mirvetuximab Soravtansine will be administered per dose and schedule specified in the arm.
DRUGPaclitaxel
Paclitaxel will be administered per dose and schedule specified in the arm.
DRUGPegylated liposomal doxorubicin
Pegylated liposomal doxorubicin will be administered per dose and schedule specified in the arm.
DRUGTopotecan
Topotecan will be administered per dose and schedule specified in the arm.
Sponsors
Gynecologic Oncology Group
ImmunoGen, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must be diagnosed with advanced epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer * Participants must have folate receptor alpha positive tumor expression as defined in the protocol * Participants must have platinum-resistant ovarian cancer, defined as progression within 6 months from completion of a minimum of four cycles of platinum-containing therapy. * Participants must have received at least one but no more than three prior systemic treatment regimens and for whom single-agent chemotherapy is appropriate as the next line of treatment * Participants must have at least one lesion that meets the definition of measurable disease by RECIST 1.1
Exclusion criteria
* Diagnosis of clear cell, low grade ovarian cancer or mixed tumors * Participants with primary platinum-refractory disease * Serious concurrent illness or clinically relevant active infection as defined in the protocol * Prior treatment with mirvetuximab soravtansine * Women who are pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS), as Assessed by BIRC Per RECIST Version 1.1 in All Participants Randomized to the Study | From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm) | PFS was defined as the time from randomization until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the sum of the longest diameters (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. |
| PFS, as Assessed by BIRC Per RECIST Version 1.1 in Participants With High Folate Receptor Alpha Level (≥ 75% of Tumor Staining) | From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm) | PFS was defined as the time from randomization 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving at Least a 15% (≥ 15-Point) Absolute Improvement From Baseline on the EORTC QLQ-OV28 Abdominal/Gastrointestinal (AB/GI) Symptom Subscale at Week 8/9 Assessment | Baseline, Week 8/9 | European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer 28 (EORTC QLQ-OV28) is a 28-item ovarian cancer supplemental module. It comprises of 6 symptom scales (AB/GI symptoms, peripheral neuropathy, other chemotherapy side-effects, hormonal symptoms, body image, attitude to disease, treatment), and sexual functioning. Participants were asked to indicate extent to which they experienced AB/GI symptoms. Participants responded on a scale of 1-4(1=not at all, 2=a little, 3=quite a bit, 4=very much) to following: Did you have abdominal pain? Did you have a bloated feeling in your abdomen? Did you have problems with your clothes feeling too tight? Did you experience any change in bowel habit as a result of your disease or treatment? Were you troubled by passing wind/gas/flatulence? Have you felt full too quickly after beginning to eat? Have you had indigestion/heartburn? Data were transformed to a scale from 0-100. Lower scores=better health. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm) | Adverse event (AE): 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: graded per National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) v4.03 on following scale: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death. Relation of AE to treatment was determined by investigator. Serious AEs: death, life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent/significant disability or incapacity, congenital anomaly or birth defect, or an important medical event that required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: any AE that emerged on or after the first dose, and within 30 days of the last dose. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported AEs module. |
| Gynecologic Cancer Intergroup (GCIG) CA-125 Response Rate: Percentage of Participants With GCIG CA-125 Confirmed Clinical Responses | From first dose of study drug until CA-125 response (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm) | CA-125 Response rate wasdefined as the number of participants with a CA-125 confirmed response divided by the number of participants in the CA-125 response-evaluable population multiplied by 100. |
| Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by BIRC Per RECIST1.1 | From randomization until first BOR of CR or PR (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm) | 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 SoD of target lesions, taking as reference the baseline SoD. |
| Duration of Response (DOR), as Assessed by BIRC Per RECIST v1.1 | From the date of first response (CR or PR) until the date of PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm) | DOR was defined as the time from the date of the first response (CR or PR), whichever was recorded first, until the date of 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. |
| Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4 | Pre-dose and within 5 minutes after mirvetuximab soravtansine infusion on Day 1 of Cycles 1 and 3; and Day 8 and 15 of Cycles 1 and 3 | PK parameters were calculated using standard non-compartmental methods. |
| Number of Participants With Anti-Drug Antibodies (ADA) | Pre-dose and within 5 minutes after mirvetuximab soravtansine infusion on Day 1 of Cycles 1, 2, and 4; pre-dose on Day 1 of Cycle 6 | An electrochemiluminescent method was used for the detection of anti-mirvetuximab soravtansine antibodies in plasma from samples collected in dipotassium ethylenediaminetetraacetic acid (K2EDTA) tubes. The qualitative assay was designed to detect anti-mirvetuximab soravtansine antibodies in human plasma. |
| PFS, as Assessed by Investigator Per RECIST Version 1.1 | From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm) | PFS was defined as the time from randomization 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. |
| Overall Survival (OS) | From the date of randomization until the time of death (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm) | OS was defined as the time from the date of randomization until the date of death from any cause. Participants who did not experience the event of death were censored at their last date known to be alive. OS was estimated using the Kaplan-Meier method. |
Countries
Belgium, Bosnia and Herzegovina, Canada, Czechia, France, Ireland, Italy, Russia, Serbia, Spain, Switzerland, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 366 participants were randomized in 2:1 to receive either mirvetuximab soravtansine or the investigator's choice (IC) chemotherapy.
Participants by arm
| Arm | Count |
|---|---|
| Mirvetuximab Soravtansine Participants received mirvetuximab soravtansine at 6 mg/kg AIBW administered IV on Day 1 of a 3 week cycle. Participants continued to receive study drug until they experienced PD per RECIST version 1.1 (as assessed by BIRC), experienced unacceptable toxicity, or withdrew consent, whichever came first, or until the sponsor terminated the study. (Maximum exposure: 86.9 weeks) | 248 |
| Investigator's Choice (IC) Chemotherapy Participants received a dose of IC chemotherapeutic agent calculated using BSA. Paclitaxel administered at 80 mg/m\^2 as a 1-hour IV infusion on Days 1, 8, 15, and 22 of a 4-week cycle; or topotecan administered at 4 mg/m\^2 over 30 minutes on Days 1, 8, and 15 of a 4-week cycle. Alternatively, topotecan could have been administered at 1.25 mg/m\^2 over 30 minutes on Days 1 to 5 of a 3-week cycle; or pegylated liposomal doxorubicin administered at 40 mg/m\^2 as a 1 mg/minute IV infusion on Day 1 of a 4-week cycle. After Cycle 1, if tolerated, pegylated liposomal doxorubicin could have been administered as a 1-hour infusion. Participants continued to receive study drug until they experienced PD per RECIST version 1.1 (as assessed by BIRC), experienced unacceptable toxicity, or withdrew consent, whichever came first, or until the sponsor terminated the study. (Maximum exposure: 62.9 weeks) | 118 |
| Total | 366 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 96 | 50 |
| Overall Study | Investigator's discretion | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Other than specified | 4 | 4 |
| Overall Study | Withdrawal by Subject | 16 | 9 |
Baseline characteristics
| Characteristic | Investigator's Choice (IC) Chemotherapy | Total | Mirvetuximab Soravtansine |
|---|---|---|---|
| Age, Continuous | 62.9 years STANDARD_DEVIATION 10.51 | 62.8 years STANDARD_DEVIATION 10.35 | 62.7 years STANDARD_DEVIATION 10.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 21 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 102 Participants | 327 Participants | 225 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 18 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 8 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 10 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 13 Participants | 8 Participants |
| Race (NIH/OMB) White | 105 Participants | 330 Participants | 225 Participants |
| Sex: Female, Male Female | 118 Participants | 366 Participants | 248 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 96 / 243 | 50 / 109 |
| other Total, other adverse events | 242 / 243 | 106 / 109 |
| serious Total, serious adverse events | 67 / 243 | 31 / 109 |
Outcome results
Primary
PFS, as Assessed by BIRC Per RECIST Version 1.1 in Participants With High Folate Receptor Alpha Level (≥ 75% of Tumor Staining)
PFS was defined as the time from randomization 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 the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Population: ITT population included all participants randomized in the study. Here, overall number of participants analyzed signifies participants with high folate receptor alpha level.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mirvetuximab Soravtansine | PFS, as Assessed by BIRC Per RECIST Version 1.1 in Participants With High Folate Receptor Alpha Level (≥ 75% of Tumor Staining) | 4.76 months |
| Investigator's Choice (IC) Chemotherapy | PFS, as Assessed by BIRC Per RECIST Version 1.1 in Participants With High Folate Receptor Alpha Level (≥ 75% of Tumor Staining) | 3.25 months |
Primary
Progression-Free Survival (PFS), as Assessed by BIRC Per RECIST Version 1.1 in All Participants Randomized to the Study
PFS was defined as the time from randomization until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the sum of the longest diameters (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 the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Population: ITT population included all participants randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mirvetuximab Soravtansine | Progression-Free Survival (PFS), as Assessed by BIRC Per RECIST Version 1.1 in All Participants Randomized to the Study | 4.14 months |
| Investigator's Choice (IC) Chemotherapy | Progression-Free Survival (PFS), as Assessed by BIRC Per RECIST Version 1.1 in All Participants Randomized to the Study | 4.44 months |
Secondary
Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4
PK parameters were calculated using standard non-compartmental methods.
Time frame: Pre-dose and within 5 minutes after mirvetuximab soravtansine infusion on Day 1 of Cycles 1 and 3; and Day 8 and 15 of Cycles 1 and 3
Population: PK population included all participants who received at least 1 infusion of mirvetuximab soravtansine, had evaluable PK data, and had samples collected with no major deviations related to administration of study drug. Here, 'number analyzed'=participants evaluable for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirvetuximab Soravtansine | Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4 | S-methyl DM4 at Cycle 1 | 1586 hours*milligrams/milliliter (hr*mg/mL) | Standard Deviation 1496 |
| Mirvetuximab Soravtansine | Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4 | S-methyl DM4 at Cycle 3 | 1512 hours*milligrams/milliliter (hr*mg/mL) | Standard Deviation 1278 |
| Mirvetuximab Soravtansine | Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4 | Mirvetuximab Soravtansine at Cycle 1 | 20.53 hours*milligrams/milliliter (hr*mg/mL) | Standard Deviation 10.31 |
| Mirvetuximab Soravtansine | Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4 | Mirvetuximab Soravtansine at Cycle 3 | 22.40 hours*milligrams/milliliter (hr*mg/mL) | Standard Deviation 7.77 |
| Mirvetuximab Soravtansine | Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4 | Total M9346A antibody at Cycle 1 | 23.23 hours*milligrams/milliliter (hr*mg/mL) | Standard Deviation 9.463 |
| Mirvetuximab Soravtansine | Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4 | Total M9346A antibody at Cycle 3 | 31.20 hours*milligrams/milliliter (hr*mg/mL) | Standard Deviation 11.52 |
| Mirvetuximab Soravtansine | Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4 | DM4 at Cycle 1 | 348.5 hours*milligrams/milliliter (hr*mg/mL) | Standard Deviation 265.7 |
| Mirvetuximab Soravtansine | Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4 | DM4 at Cycle 3 | 347.4 hours*milligrams/milliliter (hr*mg/mL) | Standard Deviation 280.9 |
Secondary
Duration of Response (DOR), as Assessed by BIRC Per 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 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: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Population: ITT population included all participants randomized in the study. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mirvetuximab Soravtansine | Duration of Response (DOR), as Assessed by BIRC Per RECIST v1.1 | 5.65 months |
| Investigator's Choice (IC) Chemotherapy | Duration of Response (DOR), as Assessed by BIRC Per RECIST v1.1 | 7.26 months |
Secondary
Gynecologic Cancer Intergroup (GCIG) CA-125 Response Rate: Percentage of Participants With GCIG CA-125 Confirmed Clinical Responses
CA-125 Response rate wasdefined as the number of participants with a CA-125 confirmed response divided by the number of participants in the CA-125 response-evaluable population multiplied by 100.
Time frame: From first dose of study drug until CA-125 response (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Population: CA-125-Evaluable population included all randomized population whose pretreatment sample was ≥ 2.0 times the upper limit of normal (ULN), within 2 weeks prior to randomization, and who had at least 1 post-baseline CA 125 evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mirvetuximab Soravtansine | Gynecologic Cancer Intergroup (GCIG) CA-125 Response Rate: Percentage of Participants With GCIG CA-125 Confirmed Clinical Responses | 51 percentage of participants |
| Investigator's Choice (IC) Chemotherapy | Gynecologic Cancer Intergroup (GCIG) CA-125 Response Rate: Percentage of Participants With GCIG CA-125 Confirmed Clinical Responses | 27 percentage of participants |
Secondary
Number of Participants Achieving at Least a 15% (≥ 15-Point) Absolute Improvement From Baseline on the EORTC QLQ-OV28 Abdominal/Gastrointestinal (AB/GI) Symptom Subscale at Week 8/9 Assessment
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer 28 (EORTC QLQ-OV28) is a 28-item ovarian cancer supplemental module. It comprises of 6 symptom scales (AB/GI symptoms, peripheral neuropathy, other chemotherapy side-effects, hormonal symptoms, body image, attitude to disease, treatment), and sexual functioning. Participants were asked to indicate extent to which they experienced AB/GI symptoms. Participants responded on a scale of 1-4(1=not at all, 2=a little, 3=quite a bit, 4=very much) to following: Did you have abdominal pain? Did you have a bloated feeling in your abdomen? Did you have problems with your clothes feeling too tight? Did you experience any change in bowel habit as a result of your disease or treatment? Were you troubled by passing wind/gas/flatulence? Have you felt full too quickly after beginning to eat? Have you had indigestion/heartburn? Data were transformed to a scale from 0-100. Lower scores=better health.
Time frame: Baseline, Week 8/9
Population: ITT population included all participants randomized in the study. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mirvetuximab Soravtansine | Number of Participants Achieving at Least a 15% (≥ 15-Point) Absolute Improvement From Baseline on the EORTC QLQ-OV28 Abdominal/Gastrointestinal (AB/GI) Symptom Subscale at Week 8/9 Assessment | 45 Participants |
| Investigator's Choice (IC) Chemotherapy | Number of Participants Achieving at Least a 15% (≥ 15-Point) Absolute Improvement From Baseline on the EORTC QLQ-OV28 Abdominal/Gastrointestinal (AB/GI) Symptom Subscale at Week 8/9 Assessment | 7 Participants |
Secondary
Number of Participants With Anti-Drug Antibodies (ADA)
An electrochemiluminescent method was used for the detection of anti-mirvetuximab soravtansine antibodies in plasma from samples collected in dipotassium ethylenediaminetetraacetic acid (K2EDTA) tubes. The qualitative assay was designed to detect anti-mirvetuximab soravtansine antibodies in human plasma.
Time frame: Pre-dose and within 5 minutes after mirvetuximab soravtansine infusion on Day 1 of Cycles 1, 2, and 4; pre-dose on Day 1 of Cycle 6
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) |
|---|---|---|
| Mirvetuximab Soravtansine | Number of Participants With Anti-Drug Antibodies (ADA) | 13 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Adverse event (AE): 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: graded per National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) v4.03 on following scale: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death. Relation of AE to treatment was determined by investigator. Serious AEs: death, life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent/significant disability or incapacity, congenital anomaly or birth defect, or an important medical event that required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: any AE that emerged on or after the first dose, and within 30 days of the last dose. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported AEs module.
Time frame: From first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Population: Safety population included all enrolled participants who received at least 1 dose of mirvetuximab soravtansine or IC chemotherapy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mirvetuximab Soravtansine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 242 Participants |
| Investigator's Choice (IC) Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 107 Participants |
Secondary
Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by BIRC Per RECIST1.1
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 SoD of target lesions, taking as reference the baseline SoD.
Time frame: From randomization until first BOR of CR or PR (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Population: ITT population included all participants randomized in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mirvetuximab Soravtansine | Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by BIRC Per RECIST1.1 | 22 percentage of participants |
| Investigator's Choice (IC) Chemotherapy | Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by BIRC Per RECIST1.1 | 12 percentage of participants |
Secondary
Overall Survival (OS)
OS was defined as the time from the date of randomization until the date of death from any cause. Participants who did not experience the event of death were censored at their last date known to be alive. OS was estimated using the Kaplan-Meier method.
Time frame: From the date of randomization until the time of death (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Population: ITT population included all participants randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mirvetuximab Soravtansine | Overall Survival (OS) | 15.57 months |
| Investigator's Choice (IC) Chemotherapy | Overall Survival (OS) | 13.93 months |
Secondary
PFS, as Assessed by Investigator Per RECIST Version 1.1
PFS was defined as the time from randomization 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 the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Population: ITT population included all participants randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mirvetuximab Soravtansine | PFS, as Assessed by Investigator Per RECIST Version 1.1 | 4.27 months |
| Investigator's Choice (IC) Chemotherapy | PFS, as Assessed by Investigator Per RECIST Version 1.1 | 4.24 months |