Clinical trial NCT02606305: Study of Mirvetuximab Soravtansine in Combination With Bevacizumab, Carboplatin, Pegylated Liposomal Doxorubicin, Pembrolizumab, or Bevacizumab + Carboplatin in Participants With Folate Receptor Alpha (FRα) Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal, or Fallopian Tube Cancer
Official title: A Phase 1b/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Mirvetuximab Soravtansine (IMGN853) in Combination With Bevacizumab, Carboplatin, Pegylated Liposomal Doxorubicin, Pembrolizumab, or Bevacizumab + Carboplatin, in Adults With Folate Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Epithelial Ovarian Cancer
Primary Peritoneal Cancer
Fallopian Tube Cancer
Keywords: Epithelial ovarian cancer
Fallopian tube cancer
Primary peritoneal cancer
IMGN853
ADC
Antibody drug conjugate
ImmunoGen
Antibody
Phase 1
Folate receptor alpha
Mirvetuximab
Lead sponsor: ImmunoGen, Inc.
Sponsor class: INDUSTRY
First posted: 2015-11-17
Enrollment: 264
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study comprises a Dose Escalation phase followed by a Dose Expansion phase. Dose Escalation part of the study will assess the safety and tolerability and determine the maximum tolerated dose (MTD) as the recommended Phase 2 (RP2D) dose for each regimen. Participants will be assigned to one of the 4 regimens in Dose Escalation phase: Regimen A: mirvetuximab soravtansine administered with bevacizumab; Regimen B: mirvetuximab soravtansine administered with carboplatin; Regimen C: mirvetuximab soravtansine administered with pegylated liposomal doxorubicin; or Regimen D: mirvetuximab soravtansine administered with pembrolizumab. Dose Expansion of the study will further assess safety, tolerability and preliminary anti-tumor activity of mirvetuximab soravtansine. A Dose Expansion phase is planned for Regimen A and Regimen D and will open pending Sponsor decision; participants enrolled in the Dose Expansion phase will receive study treatment at the MTD or RP2D determined during Dose Escalation. For Regimen A, participants in the Dose Expansion phase may be enrolled according to prior exposure to bevacizumab into 3 Dose Expansion Cohorts as follows: 1) Dose Expansion Cohort 1: bevacizumab naïve; 2) Dose Expansion Cohort 2: bevacizumab pretreated; and 3) Dose Expansion Cohort 3: one to three prior treatments, one of which could have been bevacizumab. A triplet Regimen (Regimen E: mirvetuximab soravtansine + bevacizumab + carboplatin) will be opened to evaluate the safety and tolerability and to assess any early signs of activity in participants dosed with the combination regimen. All mirvetuximab soravtansine doses were calculated according to adjusted ideal body weight.

Detailed description: Participants will continue to receive mirvetuximab soravtansine and/or the combination agent until progressive disease (PD), unacceptable toxicity, or withdrawal of consent, whichever comes first, or until the Sponsor terminates the study.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with advanced epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
* Folate receptor α (FRα) positive tumor expression as defined in the protocol
* Willing to provide an archival tumor tissue block or slides or undergo tumor biopsy. New tumor biopsy (Cycle 2 Day 8) is required for Regimen D.
* Measurable disease

Exclusion Criteria:

* Primary platinum-refractory disease
* Diagnosis of clear cell, low grade ovarian cancer or mixed tumors
* Serious concurrent illness or clinically relevant active infection, including but not limited to known diagnosis of human immunodeficiency virus (HIV) and hepatitis B or C, as defined in the protocol
* Active autoimmune disease requiring systemic therapy in past 2 years (for Regimen D only)
* Women who are pregnant or breastfeeding
* Male participants

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 238.3 weeks)
measure: Dose Expansion (Regimens A and D) and Triplet (Regimen E): Objective Response Rate (ORR); Percentage of Participants With Confirmed Response, as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: From first dose of study drug until first CR or PR (maximum exposure: 238.3 weeks)
Secondary outcomes:
measure: Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1
timeFrame: From first dose of study drug until first CR or PR (maximum exposure: 238.3 weeks)
measure: Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1
timeFrame: From first dose of study drug until the date of PD or death by any cause (maximum exposure: 238.3 weeks)
measure: Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment
timeFrame: From the date of first objective response to the time of PD (maximum exposure: 238.3 weeks)
measure: Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment
timeFrame: From first dose of study drug until first CR or PR (maximum exposure: 238.3 weeks)
measure: Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody
timeFrame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of end of infusion [EOI], and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
measure: PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4)
timeFrame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of end of infusion [EOI], and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
measure: PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody
timeFrame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
measure: PK Parameter: AUCinf of Intact DM4 and SmDM4
timeFrame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
measure: PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4
timeFrame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (up to 336 hours) (additionally at Day 22 for Regimen C)
measure: PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody
timeFrame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
measure: PK Parameter: CL of DM4 and SmDM4
timeFrame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
measure: PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4
timeFrame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C)
measure: PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4
timeFrame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (up to 336 hours) (additionally at Day 22 for Regimen C)
measure: Plasma Concentration of Bevacizumab
timeFrame: At end of infusion (EOI) of Cycle 1; and at pre-infusion and EOI of Cycles 2 to 6
measure: Plasma Concentration of Carboplatin
timeFrame: At end of infusion, 6 and 24 hours post-infusion of Cycle 1; and at pre-infusion and end of infusion of Cycles 2, 4, 5 and 6; at pre-infusion, end of infusion and 6 and 24 hours post-infusion of Cycle 3
measure: Plasma Concentration of Pegylated Liposomal Doxorubicin
timeFrame: At end of infusion of Cycle 1; and at pre-infusion and end of infusion of Cycles 2 to 6
measure: Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) Response to Mirvetuximab Soravtansine
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 283.3 weeks)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Reno
country: United States
facility: City of Hope
state: Nevada
city: Hilliard
country: United States
facility: The Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Peggy and Charles Stephenson Oklahoma Cancer Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg - Leuvens Kankerinstituut
city: Montreal
country: Canada
facility: Centre Hospitalier de l'universite de Montreal (CHUM)
city: Montreal
country: Canada
facility: McGill University Health Center
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
city: Madrid
country: Spain
facility: MD Anderson
Study officials:
References: