Trial Outcomes & Findings for A Study of Mirvetuximab Soravtansine vs. Investigator's Choice of Chemotherapy in Women With Folate Receptor (FR) Alpha Positive Advanced Epithelial Ovarian Cancer (EOC), Primary Peritoneal or Fallopian Tube Cancer (NCT NCT02631876)

Last Updated: 2020-10-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

366 participants

Primary outcome timeframe

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)

Results posted on

2020-10-14

Participant Flow

A total of 366 participants were randomized in 2:1 to receive either mirvetuximab soravtansine or the investigator's choice (IC) chemotherapy.

Participant milestones

Participant milestones
Measure	Mirvetuximab Soravtansine Participants received mirvetuximab soravtansine at 6 milligrams/kilogram (mg/kg) adjusted ideal body weight (AIBW) administered intravenously (IV) on Day 1 of a 3 week cycle. Participants continued to receive study drug until they experienced progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (as assessed by the blinded independent review committee \[BIRC\]), experienced unacceptable toxicity, or withdrew consent, whichever came first, or until the sponsor terminated the study. (Maximum exposure: 86.9 weeks)	Investigator's Choice (IC) Chemotherapy Participants received a dose of IC chemotherapeutic agent calculated using body surface area (BSA). Paclitaxel administered at 80 milligrams/square meter (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)
Overall Study STARTED	248	118
Overall Study Safety Population	243	109
Overall Study COMPLETED	129	55
Overall Study NOT COMPLETED	119	63

Reasons for withdrawal

Reasons for withdrawal
Measure	Mirvetuximab Soravtansine Participants received mirvetuximab soravtansine at 6 milligrams/kilogram (mg/kg) adjusted ideal body weight (AIBW) administered intravenously (IV) on Day 1 of a 3 week cycle. Participants continued to receive study drug until they experienced progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (as assessed by the blinded independent review committee \[BIRC\]), experienced unacceptable toxicity, or withdrew consent, whichever came first, or until the sponsor terminated the study. (Maximum exposure: 86.9 weeks)	Investigator's Choice (IC) Chemotherapy Participants received a dose of IC chemotherapeutic agent calculated using body surface area (BSA). Paclitaxel administered at 80 milligrams/square meter (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)
Overall Study Death	96	50
Overall Study Investigator's discretion	1	0
Overall Study Lost to Follow-up	2	0
Overall Study Withdrawal by Subject	16	9
Overall Study Other than specified	4	4

Baseline Characteristics

A Study of Mirvetuximab Soravtansine vs. Investigator's Choice of Chemotherapy in Women With Folate Receptor (FR) Alpha Positive Advanced Epithelial Ovarian Cancer (EOC), Primary Peritoneal or Fallopian Tube Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mirvetuximab Soravtansine n=248 Participants 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)	Investigator's Choice (IC) Chemotherapy n=118 Participants 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)	Total n=366 Participants Total of all reporting groups
Age, Continuous	62.7 years STANDARD_DEVIATION 10.29 • n=5 Participants	62.9 years STANDARD_DEVIATION 10.51 • n=7 Participants	62.8 years STANDARD_DEVIATION 10.35 • n=5 Participants
Sex: Female, Male Female	248 Participants n=5 Participants	118 Participants n=7 Participants	366 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	225 Participants n=5 Participants	102 Participants n=7 Participants	327 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) White	225 Participants n=5 Participants	105 Participants n=7 Participants	330 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mirvetuximab Soravtansine n=248 Participants 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)	Investigator's Choice (IC) Chemotherapy n=118 Participants 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)
Progression-Free Survival (PFS), as Assessed by BIRC Per RECIST Version 1.1 in All Participants Randomized to the Study	4.14 months Interval 3.75 to 4.53	4.44 months Interval 2.83 to 5.59

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Mirvetuximab Soravtansine n=147 Participants 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)	Investigator's Choice (IC) Chemotherapy n=71 Participants 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)
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 Interval 4.11 to 5.68	3.25 months Interval 1.97 to 5.59

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Mirvetuximab Soravtansine n=248 Participants 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)	Investigator's Choice (IC) Chemotherapy n=118 Participants 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)
Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by BIRC Per RECIST1.1	22 percentage of participants Interval 17.2 to 27.9	12 percentage of participants Interval 6.6 to 19.1

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Mirvetuximab Soravtansine n=248 Participants 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)	Investigator's Choice (IC) Chemotherapy n=118 Participants 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)
Overall Survival (OS)	15.57 months Interval 12.85 to 18.04	13.93 months Interval 11.4 to 18.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Mirvetuximab Soravtansine n=142 Participants 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)	Investigator's Choice (IC) Chemotherapy n=50 Participants 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)
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	7 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Mirvetuximab Soravtansine n=243 Participants 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)	Investigator's Choice (IC) Chemotherapy n=109 Participants 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)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	242 Participants	107 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Mirvetuximab Soravtansine n=203 Participants 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)	Investigator's Choice (IC) Chemotherapy n=82 Participants 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)
Gynecologic Cancer Intergroup (GCIG) CA-125 Response Rate: Percentage of Participants With GCIG CA-125 Confirmed Clinical Responses	51 percentage of participants Interval 44.1 to 58.3	27 percentage of participants Interval 17.6 to 37.8

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mirvetuximab Soravtansine n=248 Participants 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)	Investigator's Choice (IC) Chemotherapy n=118 Participants 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)
PFS, as Assessed by Investigator Per RECIST Version 1.1	4.27 months Interval 4.11 to 5.06	4.24 months Interval 2.76 to 5.36

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Mirvetuximab Soravtansine n=55 Participants 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)	Investigator's Choice (IC) Chemotherapy n=14 Participants 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)
Duration of Response (DOR), as Assessed by BIRC Per RECIST v1.1	5.65 months Interval 4.17 to 8.51	7.26 months Interval 4.14 to Data not calculated due to less number of participants with an event

SECONDARY outcome

Timeframe: 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.

PK parameters were calculated using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Mirvetuximab Soravtansine n=235 Participants 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)	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)
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 hoursmilligrams/milliliter (hrmg/mL) Standard Deviation 10.31	—
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 hoursmilligrams/milliliter (hrmg/mL) Standard Deviation 7.770	—
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 hoursmilligrams/milliliter (hrmg/mL) Standard Deviation 9.463	—
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 hoursmilligrams/milliliter (hrmg/mL) Standard Deviation 11.52	—
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 hoursmilligrams/milliliter (hrmg/mL) Standard Deviation 265.7	—
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 hoursmilligrams/milliliter (hrmg/mL) Standard Deviation 280.9	—
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 hoursmilligrams/milliliter (hrmg/mL) Standard Deviation 1496	—
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 hoursmilligrams/milliliter (hrmg/mL) Standard Deviation 1278	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Mirvetuximab Soravtansine n=230 Participants 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)	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)
Number of Participants With Anti-Drug Antibodies (ADA)	13 Participants	—

Adverse Events

Mirvetuximab Soravtansine

Serious events: 67 serious events

Other events: 242 other events

Deaths: 96 deaths

Investigator's Choice (IC) Chemotherapy

Serious events: 31 serious events

Other events: 106 other events

Deaths: 50 deaths

Serious adverse events

Other adverse events

Additional Information

CMO, ImmunoGen

ImmunoGen, Inc

Phone: 781-895-0600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place