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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

NCT02606305

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT02606305

Trial Eligibility

Document

Title

  • Brief Title: Study of Mirvetuximab Soravtansine in Comb. With Bevacizumab, Carboplatin, PLD, Pembrolizumab, or Bevacizumab + Carboplatin in Adults With FRa + Adv. EOC, 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

Clinical Trial IDs

  • ORG STUDY ID: IMGN853-0402
  • SECONDARY ID: KEYNOTE PN409
  • NCT ID: NCT02606305

Conditions

  • Epithelial Ovarian Cancer
  • Primary Peritoneal Cancer
  • Fallopian Tube Cancer

Interventions

DrugSynonymsArms
IMGN853Regimen A
BevacizumabRegimen A
CarboplatinRegimen B
Pegylated Liposomal DoxorubicinRegimen C
PembrolizumabRegimen D
Bevacizumab+CarboplatinRegimen E

Purpose

This is a phase 1b/2 study to assess the safety, tolerability, and preliminary anti-tumor activity of IMGN853 when administered with chemotherapy. Patients will be assigned to one of five regimens: IMGN853 administered with bevacizumab, IMGN853 administered with carboplatin, IMGN853 administered with pegylated liposomal doxorubicin, IMGN853 administered with pembrolizumab, or IMGN853 administered with bevacizumab+carboplatin

Detailed Description

      The dose escalation part of the study will assess safety and tolerability and determine the
      maximum tolerated dose (MTD) for each regimen. The dose expansion of the MTD will assess
      safety, tolerability and preliminary anti-tumor activity.

Trial Arms

NameTypeDescriptionInterventions
Regimen AExperimentalDose escalation and dose expansion with IMGN853 and bevacizumab
  • IMGN853
  • Bevacizumab
Regimen BExperimentalDose Escalation with IMGN853 and carboplatin
  • IMGN853
  • Carboplatin
Regimen CExperimentalDose Escalation with IMGN853 and pegylated liposomal doxorubicin
  • IMGN853
  • Pegylated Liposomal Doxorubicin
Regimen DExperimentalDose escalation and dose expansion with IMGN853 and pembrolizumab
  • IMGN853
  • Pembrolizumab
Regimen EExperimentalDose expansion with IMGN853 and bevacizumab+carboplatin
  • IMGN853
  • Bevacizumab+Carboplatin

Eligibility Criteria

        Inclusion Criteria:

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

          -  Folate receptor alpha positive tumor expression as defined in the protocol

          -  Willing to undergo tumor biopsy

          -  Measurable disease

        Exclusion Criteria:

          -  Primary platinum-refractory EOC

          -  Diagnosis of clear cell, low grade ovarian cancer or mixed tumors

          -  Serious concurrent illness or clinically relevant active infection, including known
             diagnosis of HIV and hepatitis B or C, as defined in the protocol

          -  Active autoimmune disease requiring systemic therapy in past 2 years (IMGN853 and
             pembrolizumab only)

          -  Women who are pregnant or breastfeeding

          -  Male patients
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of TEAEs, SAEs, adverse events, clinically significant changes in laboratory/clinical tests and dose-limiting toxicities (DLTs) as a measure of safety and tolerability [dose escalation]
Time Frame:Up to 2.5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of response (DOR); the time from first objective response until progressive disease, will be calculated for all patients who achieve a confirmed objective response (PR or CR)
Time Frame:Up to 2.5 years
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:PK parameters: maximum plasma concentration (Cmax) of IMGN853, bevacizumab, carboplatin and PLD
Time Frame:Up to 2.5 years
Safety Issue:
Description:
Measure:PK parameters: area under the time-concentration curve (AUC) of IMGN853, bevacizumab, carboplatin and PLD
Time Frame:Up to 2.5 years
Safety Issue:
Description:
Measure:PK parameters: terminal half-life (t½) of IMGN853, bevacizumab, carboplatin and PLD
Time Frame:Up to 2.5 years
Safety Issue:
Description:
Measure:PK parameters: clearance (Cl) of IMGN853, bevacizumab, carboplatin and PLD
Time Frame:Up to 2.5 years
Safety Issue:
Description:
Measure:PK parameters: volume of distribution at steady state (Vss) of IMGN853, bevacizumab, carboplatin and PLD
Time Frame:Up to 2.5 years
Safety Issue:
Description:
Measure:PK parameters: maximum time (Tmax) of IMGN853, bevacizumab, carboplatin and PLD
Time Frame:Up to 2.5 years
Safety Issue:
Description:
Measure:Immunogenicity: Presence of Anti-Drug Antibody (ADA)
Time Frame:Up to 2.5 years
Safety Issue:
Description:
Measure:Number of patients with CA125 clinical response.
Time Frame:Up to 2.5 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:ImmunoGen, Inc.

Trial Keywords

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

Last Updated

September 10, 2019