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
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
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) |
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Abstract Disclosures
2023 ASCO Annual Meeting
First Author: Debra L. Richardson
2020 ASCO Virtual Scientific Program
First Author: Lucy Gilbert
2019 ASCO Annual Meeting
First Author: David M. O'Malley
2023 ASCO Annual Meeting
First Author: Yoo Na Kim