Phase 2
Completed N=62
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
epithelial ovarian cancer · Primary Peritoneal Cancer · Fallopian tube cancer
Source: ClinicalTrials.gov NCT02606305 ↗
Enrolled (actual)
62
Serious AEs
41.7%
Results posted
Feb 2024
Primary outcomePrimary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) — 3; 126; 4; 4 Participants
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. All mirvetuximab soravtansine doses were calculated according to adjusted ideal body weight.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
3; 126; 4; 4; 10; 4 | — |
| PRIMARY 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 |
52; 29; 50; 27; 83 | — |
| SECONDARY Dose Escalation (Regimens A Through D): ORR; Percentage of Participants With Confirmed Response, as Assessed by RECIST Version 1.1 |
0; 45; 50; 50; 89; 0 | — |
| SECONDARY Progression-Free Survival (PFS); Time From the Date Of First Dose Until The Date Of Progressive Disease (PD) Or Death By Any Cause, As Defined By RECIST Version 1.1 |
13.49; 8.80; 9.92; 6.77; 8.28; 13.52 | — |
| SECONDARY Duration of Response (DOR) Per RECIST v1.1 by Investigator Assessment |
NA; 11.96; 14.06; 10.38; NA; 31.77 | — |
| SECONDARY Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 Clinical Response Rate by Investigator Assessment |
100; 60; 75; 65; 71; 67 | — |
| SECONDARY Pharmacokinetics (PK) Parameter: Maximum Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total Antibody |
135; 137; 159; 159; 150; 118 | — |
| SECONDARY PK Parameter: Cmax of N2'-[4-[(3-carboxypropyl)Dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-Deacetylmaytansine (DM4) and S-methyl DM4 (SmDM4) |
3.04; 4.71; 5.51; 6.32; 5.59; 2.96 | — |
| SECONDARY PK Parameter: Area Under the Time-Concentration Curve From Time 0 To Infinite Time (AUCinf) of Mirvetuximab Soravtansine and Total Antibody |
16.1; 17; 18.6; 18.4; 17.5; 14.8 | — |
| SECONDARY PK Parameter: AUCinf of Intact DM4 and SmDM4 |
NA; 249; 253; 289; 272; 161 | — |
| SECONDARY PK Parameter: Terminal Half-Life (t½) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 |
104; 123; 124; 121; 126; 117 | — |
| SECONDARY PK Parameter: Clearance (CL) of Mirvetuximab Soravtansine and Total Antibody |
19.2; 22; 22; 20.9; 23.4; 19.9 | — |
| SECONDARY PK Parameter: CL of DM4 and SmDM4 |
NA; 29; 30.9; 25.2; 28.6; 35 | — |
| SECONDARY PK Parameter: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 |
2.93; 3.63; 3.54; 3.31; 3.87; 3.23 | — |
| SECONDARY PK Parameter: Time to Reach Cmax (Tmax) of Mirvetuximab Soravtansine, Total Antibody, DM4, and SmDM4 |
1.75; 1.9; 2.1; 1.92; 2.06; 1.68 | — |
| SECONDARY Plasma Concentration of Bevacizumab |
368; 352; 406; 430; 448; 413 | — |
| SECONDARY Plasma Concentration of Carboplatin |
10300; 1060; 13900; 11800; 2890; 3790 | — |
| SECONDARY Plasma Concentration of Pegylated Liposomal Doxorubicin |
18700; 24400; 26400; NA; 226; 17300 | — |
| SECONDARY Immunogenicity: Number of Participants With Anti-Drug Antibody (ADA) Response to Mirvetuximab Soravtansine |
51; 175; 3; 11; 7; 11 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02606305). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.