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

NCT02606305 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: IMGN853-0402KEYNOTE PN409
• Study Type: interventional
• Target: 264
• Locations: 4 countries
• Sites: 12

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.

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Adverse events (AEs) were any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function that developed or worsened during the clinical study, not necessarily having 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: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death. Serious AEs included 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 previously listed. TEAEs were any AE that emerged on or after the first dose, and within 30 days of the last dose. Serious and other non-serious AEs regardless of causality are reported in the AE module.

  From first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 238.3 weeks)

• 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

  ORR was defined as percentage of participants with confirmed response (complete response \[CR\] + 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 (SLD) of target lesions, taking as reference the baseline SLD. The 95% confidence interval (CI) was based on binomial distribution.

  From first dose of study drug until first CR or PR (maximum exposure: 238.3 weeks)

Secondary Outcomes (17)

• Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1

  From first dose of study drug until first CR or PR (maximum exposure: 238.3 weeks)

• 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

  From first dose of study drug until the date of PD or death by any cause (maximum exposure: 238.3 weeks)

• Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment

  From the date of first objective response to the time of PD (maximum exposure: 238.3 weeks)

• Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment

  From first dose of study drug until first CR or PR (maximum exposure: 238.3 weeks)

• Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody

  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)

Study Arms (5)

Regimen A (Mirvetuximab soravtansine + Bevacizumab)

EXPERIMENTAL

Mirvetuximab soravtansine + Bevacizumab administered on Day 1 of each 21-day cycle in Dose Escalation and Dose Expansion phase.

Drug: Mirvetuximab soravtansine; Drug: Bevacizumab

Regimen B (Mirvetuximab soravtansine + Carboplatin)

EXPERIMENTAL

Mirvetuximab soravtansine + Carboplatin administered on Day 1 of each 21-day cycle in Dose Escalation phase.

Drug: Mirvetuximab soravtansine; Drug: Carboplatin

Regimen C (Mirvetuximab soravtansine + Pegylated liposomal doxorubicin)

EXPERIMENTAL

Mirvetuximab soravtansine + Pegylated liposomal doxorubicin administered on Day 1 of each 28-day cycle in Dose Escalation Phase.

Drug: Mirvetuximab soravtansine; Drug: Pegylated Liposomal Doxorubicin

Regimen D (Mirvetuximab soravtansine + Pembrolizumab)

EXPERIMENTAL

Mirvetuximab soravtansine + Pembrolizumab administered on Day 1 of each 21-day cycle in Dose Escalation and Dose Expansion phase.

Drug: Mirvetuximab soravtansine; Drug: Pembrolizumab

Regimen E (Mirvetuximab soravtansine + Bevacizumab + Carboplatin)

EXPERIMENTAL

Mirvetuximab soravtansine + Bevacizumab + Carboplatin administered on Day 1 of each 21-day cycle in Dose Expansion phase.

Drug: Mirvetuximab soravtansine; Drug: Bevacizumab; Drug: Carboplatin

Interventions

Mirvetuximab soravtansine DRUG

Also known as: IMGN853

Regimen A (Mirvetuximab soravtansine + Bevacizumab); Regimen B (Mirvetuximab soravtansine + Carboplatin); Regimen C (Mirvetuximab soravtansine + Pegylated liposomal doxorubicin); Regimen D (Mirvetuximab soravtansine + Pembrolizumab); Regimen E (Mirvetuximab soravtansine + Bevacizumab + Carboplatin)

Bevacizumab DRUG

Regimen A (Mirvetuximab soravtansine + Bevacizumab); Regimen E (Mirvetuximab soravtansine + Bevacizumab + Carboplatin)

Carboplatin DRUG

Regimen B (Mirvetuximab soravtansine + Carboplatin); Regimen E (Mirvetuximab soravtansine + Bevacizumab + Carboplatin)

Pegylated Liposomal Doxorubicin DRUG

Regimen C (Mirvetuximab soravtansine + Pegylated liposomal doxorubicin)

Pembrolizumab DRUG

Regimen D (Mirvetuximab soravtansine + Pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ImmunoGen, Inc.: lead

Study Sites (12)

University of California at Los Angeles

Los Angeles, California, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

City of Hope

Reno, Nevada, United States

Location

The Ohio State University

Hilliard, Ohio, 43026, United States

Location

Peggy and Charles Stephenson Oklahoma Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg - Leuvens Kankerinstituut

Leuven, 3000, Belgium

Location

Centre Hospitalier de l'universite de Montreal (CHUM)

Montreal, Canada

Location

McGill University Health Center

Montreal, Canada

Location

Hospital Vall D'Hebron

Barcelona, Spain

Location

MD Anderson

Madrid, 28033, Spain

Location

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms

Interventions

mirvetuximab soravtansine; Bevacizumab; Carboplatin; liposomal doxorubicin; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: CMO, ImmunoGen
• Organization: ImmunoGen, Inc

clinicaltrials@immunogen.com

781-895-0600

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2015
• First Posted: November 17, 2015
• Study Start: March 2, 2016
• Primary Completion: March 12, 2021
• Study Completion: March 12, 2021
• Last Updated: June 14, 2024
• Results First Posted: February 14, 2024

Record last verified: 2024-06

Locations

CA (2); BE (1); ES (2); US (7)