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

ImmunoGen

Status and phase: Completed; Phase 2; Phase 1

Conditions: Primary Peritoneal Cancer; Epithelial Ovarian Cancer; Fallopian Tube Cancer

Treatments: Drug: Mirvetuximab soravtansine; Drug: Carboplatin; Drug: Pegylated Liposomal Doxorubicin; Drug: Pembrolizumab; Drug: Bevacizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02606305

IMGN853-0402

KEYNOTE PN409 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 264 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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264 participants in 5 patient groups

Regimen A (Mirvetuximab soravtansine + Bevacizumab)

Experimental group

Description:

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

Treatment:

Drug: Bevacizumab

Drug: Mirvetuximab soravtansine

Regimen B (Mirvetuximab soravtansine + Carboplatin)

Experimental group

Description:

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

Treatment:

Drug: Carboplatin

Drug: Mirvetuximab soravtansine

Regimen C (Mirvetuximab soravtansine + Pegylated liposomal doxorubicin)

Experimental group

Description:

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

Treatment:

Drug: Pegylated Liposomal Doxorubicin

Drug: Mirvetuximab soravtansine

Regimen D (Mirvetuximab soravtansine + Pembrolizumab)

Experimental group

Description:

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

Treatment:

Drug: Pembrolizumab

Drug: Mirvetuximab soravtansine

Regimen E (Mirvetuximab soravtansine + Bevacizumab + Carboplatin)

Experimental group

Description:

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

Treatment:

Drug: Bevacizumab

Drug: Carboplatin

Drug: Mirvetuximab soravtansine