Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-agnostic ovarian cancer: Final analysis.

Authors

null

David M. O'Malley

The Ohio State University Wexner Medical Center and James Cancer Hospital, Columbus, OH

David M. O'Malley , Ana Oaknin , Ursula A. Matulonis , Gina Mantia-Smaldone , Peter C Lim , Cesar Martin Castro , Diane M. Provencher , Sanaz Memarzadeh , Patrick A. Zweidler-McKay , Jiuzhou Wang , Brooke Esteves , Kathleen N. Moore , Lucy Gilbert

Organizations

The Ohio State University Wexner Medical Center and James Cancer Hospital, Columbus, OH, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Dana-Farber Cancer Institute, Boston, MA, Fox Chase Cancer Center, Philadelphia, PA, Center of Hope at Renown Regional Medical Center, Reno, NE, Massachusetts General Hospital/Harvard Medical School, Reading, MA, University of Montreal, Montreal, QC, Canada, University of California, Los Angeles (UCLA), Los Angeles, CA, ImmunoGen, Inc., Waltham, MA, ImmunoGen, Waltham, MA, Stephenson Cancer Center, Oklahoma City, OK, McGill University Health Centre, Royal Victoria Hospital, Montréal, QC, Canada

Research Funding

Pharmaceutical/Biotech Company
ImmunoGen

Background: Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. As part of the Phase 1b FORWARD II trial (NCT02606305), the combination of MIRV with bevacizumab (BEV) was evaluated in pts with FRα-positive (medium/high expression; ≥50%/ ≥75% of cells with PS2+ staining intensity), platinum agnostic ovarian cancer, defined as pts with either platinum resistant (PROC) (recurrence within 6 months after last platinum dose) or platinum sensitive (PSOC)responded to the last platinum therapy and did not progress within 6 months) for whom a non-platinum based doublet would be appropriate. Methods: Pts received MIRV (6 mg/kg; adjusted ideal body weight) and BEV (15 mg/kg) on Day 1 of a 21-day cycle. Responses were assessed by investigator according to RECIST 1.1 and adverse events (AEs) evaluated by CTCAE v4.03. Results: In total, 60 pts received the combination, with a median age of 60 years, a median of 2 prior lines of systemic therapy (range 1-4) and a median follow-up of 17.5 months. The cohort included 32 pts (53%) with PROC disease and 28 (47%) with PSOC disease. Objective responses were seen in 28 of 60 pts for a confirmed overall response rate (ORR) of 47% (95% CI, 34, 60), median duration of response (mDOR) of 9.7 months (95% CI 6.7, 12.9), and median progression free survival (mPFS) of 8.3 months (95% CI 5.6, 10.6). In pts with high FRα expression (n=33), the confirmed ORR was 64% (95% CI 45, 80), mDOR of 11.8 months (95% CI 6.7, 13.7), and mPFS of 10.6 months (95% CI 8.3, 13.3); efficacy results in PROC and PSOC subsets of pts with high FRα expression are shown in the table below. The most common treatment related AEs (all grade, grade 3+) were diarrhea (68%, 2%), blurred vision (63%, 2%), fatigue (58%, 7%), and nausea (57%, 0%). The most common treatment related grade 3 and 4 AEs were neutropenia and hypertension, (12%, 3% and 13%, 0%, respectively); all other grade 3+ events occurred in ≤ 10% of pts. Conclusions: The combination of MIRV with BEV demonstrates impressive anti-tumor activity with durable responses and favorable tolerability in high FRα recurrent ovarian cancer. These results build on data previously reported for MIRV/BEV in PROC patients (Gyn Oncology O’Malley, et al 2020), suggesting that MIRV has the potential to be a preferred partner for BEV in patients with high FRα recurrent ovarian cancer regardless of platinum sensitivity. Clinical trial information: NCT02606305

Efficacy Results.


All pts
High FRα
PROC High FRα
PSOC High FRα
N
60
33
17
16
Confirmed ORR (95% CI)
47% (34, 60)
64% (45, 80)
59% (33, 82)
69% (41, 89)
mDOR months (95% CI)
9.7 (6.7, 12.9)
11.8 (6.7, 13.7)
9.4 (4.0, NR)
12.9 (6.5, 15.7)
mPFS months (95% CI)
8.3 (5.6, 10.6)
10.6 (8.3, 13.3)
10.1 (5.6, 12.9)
13.3 (8.3, 18.3)

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Oral Abstract Session

Session Title

Gynecologic Cancer

Track

Gynecologic Cancer

Sub Track

Ovarian Cancer

Clinical Trial Registration Number

NCT02606305

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 5504)

DOI

10.1200/JCO.2021.39.15_suppl.5504

Abstract #

5504

Abstract Disclosures