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Trial record 1 of 1 for:    NCT02606305
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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

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ClinicalTrials.gov Identifier: NCT02606305
Recruitment Status : Active, not recruiting
First Posted : November 17, 2015
Last Update Posted : March 3, 2021
Sponsor:
Information provided by (Responsible Party):
ImmunoGen, Inc.

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 311 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
Estimated Primary Completion Date : March 8, 2021
Estimated Study Completion Date : March 8, 2021


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



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 ]


Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02606305


Locations
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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.
Investigators
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Study Director: Patrick Zweidler-McKay, MD, PhD ImmunoGen, Inc.
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Responsible Party: ImmunoGen, Inc.
ClinicalTrials.gov Identifier: NCT02606305    
Other Study ID Numbers: IMGN853-0402
KEYNOTE PN409 ( Other Identifier: Merck )
First Posted: November 17, 2015    Key Record Dates
Last Update Posted: March 3, 2021
Last Verified: March 2021

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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:
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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