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.
Title
- Brief Title: 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: 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
| Drug | Synonyms | Arms |
|---|
| Mirvetuximab soravtansine | IMGN853 | Regimen A (Mirvetuximab soravtansine + Bevacizumab) |
| Bevacizumab | | Regimen A (Mirvetuximab soravtansine + Bevacizumab) |
| Carboplatin | | Regimen B (Mirvetuximab soravtansine + Carboplatin) |
| Pegylated Liposomal Doxorubicin | | Regimen C (Mirvetuximab soravtansine + Pegylated liposomal doxorubicin) |
| Pembrolizumab | | Regimen D (Mirvetuximab soravtansine + Pembrolizumab) |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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. | - Mirvetuximab soravtansine
- Bevacizumab
|
| Regimen B (Mirvetuximab soravtansine + Carboplatin) | Experimental | Mirvetuximab soravtansine + Carboplatin administered on Day 1 of each 21-day cycle in Dose Escalation phase. | - Mirvetuximab soravtansine
- 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. | - Mirvetuximab soravtansine
- 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. | - Mirvetuximab soravtansine
- 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. | - Mirvetuximab soravtansine
- Bevacizumab
- Carboplatin
|
Eligibility 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Dose Escalation (Regimens A Through D): Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
| Time Frame: | Baseline up to approximately 5.3 years |
| Safety Issue: | |
| Description: | Confirmed response includes complete Response (CR) + partial response (PR). |
Secondary Outcome Measures
| Measure: | Dose Expansion (Regimens A and D) and Triplet (Regimen E): Number of Participants With TEAEs |
| Time Frame: | Baseline up to approximately 5.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA125 Clinical Response |
| Time Frame: | Baseline up to approximately 5.3 years |
| Safety Issue: | |
| Description: | |
| Measure: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) to Mirvetuximab Soravtansine |
| Time Frame: | Baseline up to approximately 5.3 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
March 3, 2021
