Abstract A074: Maveropepimut-S, a DPX-based immune-educating therapy, combined with Pembrolizumab and Cyclophosphamide in recurrent ovarian cancer, results from the Phase 1/2 PESCO Trial
Authors: Veneziani Ana C. , Alqaisi Husam , Millar Douglas G , Colombo Ilaria , Gonzalez-Ochoa Eduardo , Atale Swati , Msan Anthony , Quintos Judy , Ramsahai Janelle , Garg Vikas , Soberanis Pamela , Dhani Neesha C , Grant Robert C , Wang Lisa , Bowering Valerie , Lheureux Stephanie , Ohashi Pamela S , Oza Amit M 
Published: March 2024

Background: Maveropepimut-S (MVP-S) is a DPX-based immunotherapy that targets survivin-expressing tumor cells and induces a cytotoxic T cell response. Combination with Pembrolizumab (Pemb) and low-dose Cyclophosphamide (CPA) is expected to enhance immune response. This trial aims to evaluate the safety and efficacy of MVP-S, Pemb, and low-dose CPA in patients (pts) with recurrent epithelial ovarian cancer (EOC). Methods: Non-randomized, open-label, phase 1/2 study. Phase 1 escalation cohort used a 3+3 design and included platinum-resistant EOC treated at 2 MVP-S dose levels (DL). All doses were delivered subcutaneously. MVP-S DL1, elected as recommended phase 2 dose (RP2D), included a priming dose of 0.25mL followed by boosters of 0.25mL q6w. MVP-S was combined with CPA (50 mg BID every other week) and Pemb (200 mg q3w). Phase 2 comprised three expansion cohorts. Cohorts A and B allowed high-grade serous (HGSC) or endometrioid tumors sensitive and resistant to platinum, respectively. Exploratory Cohort C enrolled pts with rare EOC subtypes. The primary endpoint was overall response rate (ORR), with secondary endpoints of safety, PFS, and OS. Tumor response was assessed every 6 wks according to RECIST1.1. Activity signal in Cohort A was defined as at least 3/10 partial response (PR) or sustained (&gt;12 wks) stable disease (SD), and for Cohort B as at least 2/10 PR or sustained SD. Biopsies and blood draws were performed before and on treatment for correlative analysis, including flow cytometry, genotyping and ctDNA. The survivin-specific immune response was detected by IFN-γ production after stimulation of PBMCs with survivin peptides. Results:16 pts in the phase 1 escalation cohort (10 DL1 and 6 DL2) and 31 in the phase 2 expansion cohorts (A:11, B:10, C:10) were enrolled. The median age was 60y (range 39-78), and the median prior therapy lines received was 3 (range 1-6). The median follow-up was 14.0 months. Most frequent histologies were HGSC (68%) and clear cell carcinoma (23%). 45 pts were evaluated for safety. The most common AE was injection site reaction, observed in 33 pts (14 G1; 12 G2; 7 G3). Other AEs included fatigue (n=20), anemia (n=18), and nausea (n=16). G1 and G2 accounted for 90% of all related AEs. G3/G4 immune-related AEs occurred in 3 and 1 pts, respectively. Among 44 pts evaluable for efficacy, 1 complete response,9 PR, and 16 SD were observed (ORR 23%). In cohort A, 4/10 pts had PR, and 5/10 had SD (4 of 5 for &gt;12 wks). In cohort B, there was 1/10 PR and 3/10 sustained SD. Cohort C was composed predominantly of clear cell carcinoma, and 2/10 pts had PR, and 2/10 had SD as the best responses. Survivin peptide re-stimulation assays were conducted in 24 pts; survivin-specific immune responses were detected in 14 pts (58%) and correlated with clinical responses (PR/SD) in 13. Conclusion: Combination of MVP-S, low-dose CPA, and Pemb in EOC is well-tolerated and shows promising clinical activity. Primary efficacy endpoints were met in cohorts A and B. Survivin-specific immune responses were correlated with clinical outcomes.

Citation Format: Ana C. Veneziani, Husam Alqaisi, Douglas G Millar, Ilaria Colombo, Eduardo Gonzalez-Ochoa, Swati Atale, Anthony Msan, Judy Quintos, Janelle Ramsahai, Vikas Garg, Pamela Soberanis, Neesha C Dhani, Robert C Grant, Lisa Wang, Valerie Bowering, Stephanie Lheureux, Pamela S Ohashi, Amit M Oza. Maveropepimut-S, a DPX-based immune-educating therapy, combined with Pembrolizumab and Cyclophosphamide in recurrent ovarian cancer, results from the Phase 1/2 PESCO Trial [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A074.