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

• ClinicalTrials.gov Identifier: NCT02606305
• Recruitment Status: Completed
• First Posted: November 17, 2015
• Last Update Posted: October 12, 2021
• Sponsor: ImmunoGen, Inc.
• Information provided by (Responsible Party): ImmunoGen, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Epithelial Ovarian Cancer; Primary Peritoneal Cancer; Fallopian Tube Cancer	Drug: Mirvetuximab soravtansine; Drug: Bevacizumab; Drug: Carboplatin; Drug: Pegylated Liposomal Doxorubicin; Drug: Pembrolizumab	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 264 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 2015
• Actual Primary Completion Date: March 12, 2021
• Actual Study Completion Date: March 12, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Regimen A (Mirvetuximab soravtansine + Bevacizumab); Mirvetuximab soravtansine + Bevacizumab administered on Day 1 of each 21-day cycle in Dose Escalation and Dose Expansion phase.	Drug: Mirvetuximab soravtansine; Other Name: IMGN853; Drug: Bevacizumab
Experimental: Regimen B (Mirvetuximab soravtansine + Carboplatin); Mirvetuximab soravtansine + Carboplatin administered on Day 1 of each 21-day cycle in Dose Escalation phase.	Drug: Mirvetuximab soravtansine; Other Name: IMGN853; Drug: Carboplatin
Experimental: Regimen C (Mirvetuximab soravtansine + Pegylated liposomal doxorubicin); Mirvetuximab soravtansine + Pegylated liposomal doxorubicin administered on Day 1 of each 28-day cycle in Dose Escalation Phase.	Drug: Mirvetuximab soravtansine; Other Name: IMGN853; Drug: Pegylated Liposomal Doxorubicin
Experimental: Regimen D (Mirvetuximab soravtansine + Pembrolizumab); Mirvetuximab soravtansine + Pembrolizumab administered on Day 1 of each 21-day cycle in Dose Escalation and Dose Expansion phase.	Drug: Mirvetuximab soravtansine; Other Name: IMGN853; Drug: Pembrolizumab
Experimental: Regimen E (Mirvetuximab soravtansine + Bevacizumab + Carboplatin); Mirvetuximab soravtansine + Bevacizumab + Carboplatin administered on Day 1 of each 21-day cycle in Dose Expansion phase.	Drug: Mirvetuximab soravtansine; Other Name: IMGN853; Drug: Bevacizumab; Drug: Carboplatin

Outcome Measures

Primary Outcome Measures :

1. Dose Escalation (Regimens A Through D): Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to approximately 5.3 years ]
2. 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 [ Time Frame: From first dose of study drug until first CR or PR (up to approximately 5.3 years) ]
   Confirmed response includes complete Response (CR) + partial response (PR).

Secondary Outcome Measures :

1. Dose Expansion (Regimens A and D) and Triplet (Regimen E): Number of Participants With TEAEs [ Time Frame: Baseline up to approximately 5.3 years ]
2. Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response (CR + PR), as Assessed by RECIST Version 1.1 [ Time Frame: From first dose of study drug until first CR or PR (up to approximately 5.3 years) ]
3. Progression-Free Survival (PFS); Time From the Date of First Dose Until the Date of PD or Death by Any Cause, as Defined by RECIST Version 1.1 [ Time Frame: From first dose of study drug until the date of PD or death by any cause (up to approximately 5.3 years) ]
4. Duration of Response (DOR); the Time From First Objective Response (CR/PR) to the Time of PD Among Those who Have Achieved a PR or CR [ Time Frame: From the date of first objective response to the time of PD (up to approximately 5.3 years) ]
5. Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA125 Clinical Response [ Time Frame: Baseline up to approximately 5.3 years ]
6. PK Parameter: Maximum Plasma Concentration (Cmax) of Intact Mirvetuximab Soravtansine Antibody Drug Conjugate (ADC), Total Antibody, N2'-[4-[(3-carboxypropyl)dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-deacetylmaytansine (DM4), and S-methyl DM4 [ Time Frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of end of infusion [EOI], and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C) ]
7. PK Parameter: Area Under the Time-Concentration Curve (AUC) of Intact Mirvetuximab Soravtansine ADC, Total Antibody, DM4, and S-methyl DM4 [ Time Frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C) ]
8. PK Parameter: Terminal Half-Life (t½) of Intact Mirvetuximab Soravtansine ADC, Total Antibody, DM4, and S-methyl DM4 [ Time Frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C) ]
9. PK Parameter: Clearance (CL) of Intact Mirvetuximab Soravtansine ADC, Total Antibody, DM4, and S-methyl DM4 [ Time Frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C) ]
10. PK Parameter: Volume of Distribution at Steady State (Vss) of Intact Mirvetuximab Soravtansine ADC, Total Antibody, DM4, and S-methyl DM4 [ Time Frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C) ]
11. PK Parameter: Time to Reach Cmax (Tmax) of Intact Mirvetuximab Soravtansine ADC, Total Antibody, DM4, and S-methyl DM4 [ Time Frame: Cycles 1 and 3: Day 1 (pre-infusion, within 10 minutes of EOI, and 6 hours post-infusion); Days 2 and 3 (24- and 48-hours post-infusion); Days 8 and 15 (additionally at Day 22 for Regimen C) ]
12. Concentration of Bevacizumab, Carboplatin, and Pegylated Liposomal Doxorubicin [ Time Frame: Bevacizumab and Pegylated Liposomal Doxorubicin: Cycles 1 to 6: Day 1 (pre-infusion, within 10 minutes of EOI); Carboplatin: Cycles 1, 2, 3, 4, 5, 6: Day 1 (pre-infusion, within 10 minutes of EOI; Cycles 1, 3: Days 1 and 2 (6- and 24-hours post-infusion) ]
13. Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) to Mirvetuximab Soravtansine [ Time Frame: Baseline up to approximately 5.3 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosed with advanced epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
• 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

Contacts and Locations

Locations

United States, Alabama

University of Alabama

Birmingham, Alabama, United States

United States, California

University of California at Los Angeles

Los Angeles, California, United States

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Nevada

City of Hope

Reno, Nevada, United States

United States, Ohio

The Ohio State University

Hilliard, Ohio, United States, 43026

United States, Oklahoma

Peggy and Charles Stephenson Oklahoma Cancer Center

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

Belgium

Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg - Leuvens Kankerinstituut

Leuven, Belgium, 3000

Canada

Juravinski Cancer Center

Calgary, Canada

Tom Baker Cancer Center

Hamilton, Canada

Centre Hospitalier de l'universite de Montreal (CHUM)

Montreal, Canada

McGill University Health Center

Montreal, Canada

Princess Margaret Cancer Center

Toronto, Canada

Spain

Hospital Vall D'Hebron

Barcelona, Spain

MD Anderson

Madrid, Spain, 28033

Sponsors and Collaborators

ImmunoGen, Inc.

More Information

• Responsible Party: ImmunoGen, Inc.
• ClinicalTrials.gov Identifier: NCT02606305
• Other Study ID Numbers: IMGN853-0402; KEYNOTE PN409 ( Other Identifier: Merck )
• First Posted: November 17, 2015
• Last Update Posted: October 12, 2021
• Last Verified: October 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ImmunoGen, Inc.:

Epithelial ovarian cancer; Fallopian tube cancer; Primary peritoneal cancer; IMGN853; ADC; Antibody drug conjugate; ImmunoGen; Antibody; Phase 1; Folate receptor alpha

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Fallopian Tube Diseases; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Bevacizumab; Pembrolizumab; Carboplatin; Doxorubicin; Liposomal doxorubicin; Maytansine; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors