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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.

Tracking Information
First Submitted Date  ICMJE November 6, 2015
First Posted Date  ICMJE November 17, 2015
Last Update Posted Date March 3, 2021
Actual Study Start Date  ICMJE December 2015
Estimated Primary Completion Date March 8, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 1, 2021)
  • Dose Escalation (Regimens A Through D): Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to approximately 5.3 years ]
  • 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).
Original Primary Outcome Measures  ICMJE
 (submitted: November 13, 2015)
Number of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), incidence of adverse events, clinically significant changes in laboratory/clinical tests and dose-limiting toxicities (DLTs) as a measure of safety and tolerability. [ Time Frame: Up to 2.5 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2021)
  • Dose Expansion (Regimens A and D) and Triplet (Regimen E): Number of Participants With TEAEs [ Time Frame: Baseline up to approximately 5.3 years ]
  • 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) ]
  • 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) ]
  • 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) ]
  • Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA125 Clinical Response [ Time Frame: Baseline up to approximately 5.3 years ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) to Mirvetuximab Soravtansine [ Time Frame: Baseline up to approximately 5.3 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2015)
  • Objective response rate (ORR); the proportion of patient achieving a complete response, partial response or stable disease (CR, PR or SD) according to RECIST1.1 and CA125 evaluations [ Time Frame: Up to 2.5 years ]
  • Duration of response (DOR); the time from initial response until progressive disease, will be estimated for all patients who achieve a confirmed objective response (PR or CR) [ Time Frame: Up to 2.5 years ]
  • Progression-free survival (PFS); the time from date of first dose until the date of objective disease progression or death by any cause as defined by RECIST 1.1 [ Time Frame: Up to 2.5 years ]
  • PK parameters: maximum plasma concentration (Cmax) of IMGN853, bevacizumab, carboplatin and PLD [ Time Frame: Up to 2.5 years ]
  • PK parameters: area under the time-concentration curve (AUC) of IMGN853, bevacizumab, carboplatin and PLD [ Time Frame: Up to 2.5 years ]
  • PK parameters: terminal half-life (t½) of IMGN853, bevacizumab, carboplatin and PLD [ Time Frame: Up to 2.5 years ]
  • PK parameters: clearance (Cl) of IMGN853, bevacizumab, carboplatin and PLD [ Time Frame: Up to 2.5 years ]
  • PK parameters: volume of distribution at steady state (Vss) of IMGN853, bevacizumab, carboplatin and PLD [ Time Frame: Up to 2.5 years ]
  • PK parameters: maximum time (Tmax) of IMGN853, bevacizumab, carboplatin and PLD [ Time Frame: Up to 2.5 years ]
  • Immunogenicity: Presence of Anti-Drug Antibody (ADA) [ Time Frame: Up to 2.5 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Epithelial Ovarian Cancer
  • Primary Peritoneal Cancer
  • Fallopian Tube Cancer
Intervention  ICMJE
  • Drug: Mirvetuximab soravtansine
    Other Name: IMGN853
  • Drug: Bevacizumab
  • Drug: Carboplatin
  • Drug: Pegylated Liposomal Doxorubicin
  • Drug: Pembrolizumab
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Mirvetuximab soravtansine
    • Drug: Bevacizumab
  • Experimental: Regimen B (Mirvetuximab soravtansine + Carboplatin)
    Mirvetuximab soravtansine + Carboplatin administered on Day 1 of each 21-day cycle in Dose Escalation phase.
    Interventions:
    • Drug: Mirvetuximab soravtansine
    • 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.
    Interventions:
    • Drug: Mirvetuximab soravtansine
    • 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.
    Interventions:
    • Drug: Mirvetuximab soravtansine
    • 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.
    Interventions:
    • Drug: Mirvetuximab soravtansine
    • Drug: Bevacizumab
    • Drug: Carboplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 1, 2021)
311
Original Estimated Enrollment  ICMJE
 (submitted: November 13, 2015)
145
Estimated Study Completion Date  ICMJE March 8, 2021
Estimated Primary Completion Date March 8, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02606305
Other Study ID Numbers  ICMJE IMGN853-0402
KEYNOTE PN409 ( Other Identifier: Merck )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ImmunoGen, Inc.
Study Sponsor  ICMJE ImmunoGen, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Patrick Zweidler-McKay, MD, PhD ImmunoGen, Inc.
PRS Account ImmunoGen, Inc.
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP