Abstract AP27: A PHASE 2 STUDY OF TPIV200/HUFR-1 (A MULTI-EPITOPE FOLATE RECEPTOR ALPHA VACCINE) IN COMBINATION WITH DURVALUMAB IN PATIENTS WITH PLATINUM RESISTANT OVARIAN CANCER
Authors: Dmitriy Zamarin, Oladapo Yeku, Rosin E. O'Cearbhaill, Karen A. Cadoo, Jacqueline Gallagher, Sara Kravetz, Autumn McDonnell, Tiffany Troso-Sandoval, Paul Sabbatini, Stuart Lichtman, William Tew, Vicky Makker, Rachel N. Grisham, David M. Hyman, Carol Aghajanian, Jason Konner
Journal: Clinical Cancer Research (2019)

Abstract INTRODUCTION: Therapy with single-agent immune checkpoint inhibitors in ovarian cancer (OC) to date has demonstrated marginal benefit, calling for rational combinations. Vaccination against tumor-associated antigens (TAA's) is a potential strategy to increase therapeutic efficacy by enhancing immunogenicity. Folate receptor alpha (FRα) is overexpressed in the majority of ovarian cancers (OC) and presents a compelling antigenic target for immunotherapy. TPIV200 is a GM-CSF-adjuvanted multi-epitope peptide anti-FRα vaccine targeting the most highly-antigenic moieties of FRα, which in recent phase I studies elicited durable immune response in over 90% of patients with ovarian and breast cancer. The current phase II study sought to examine whether a combination of TPIV200 with PD-L1 inhibitor durvalumab would result in enhanced anti-tumor immunity and therapeutic efficacy in patients with advanced platinum-resistant OC. METHODS: Twenty-seven patients with platinum resistant or refractory OC were enrolled over a 10-month period. Treatment was administered in 28-day cycles. Patients were treated with TPIV200 and GM-CSF on day 1 for 6 cycles and durvalumab on days 1 and 15 at 10mg/kg for 12 cycles. Radiologic assessments were conducted every 12 weeks. Treatment was continued until completion, evidence of clinical or radiologic progression, intolerance, or withdrawal. Exploratory correlative endpoints included tissue microenvironment analyses, including expression of PD-L1 and FRα, and peripheral vaccine-specific immune responses. RESULTS: The study enrolled 27 women with advanced OC. Median age at enrollment was 64 (42-76). Median number of prior lines of therapy was 3 (range 1-8). Of these patients, 85% (23) had high grade serous OC. There were no objective responses seen on the study. PFS rate at 24 weeks was 22%, with median PFS of 12 weeks. Six patients remained on treatment beyond 24 weeks. The majority of patients post-progression went on to receive subsequent standard therapy with durable clinical benefit. At the median follow up of 15.4 months, median OS was not reached. CONCLUSIONS: TPIV200/huFR-1 and durvalumab can be safely combined in heavily-pretreated patients with platinum-resistant OC. A subset of patients exhibited durable disease stabilization. Post-immunotherapy follow up was suggestive of improved clinical benefit from standard therapies, creating a rationale for exploration of these agents in combination with chemotherapy. Citation Format: Dmitriy Zamarin, Oladapo Yeku, Rosin E. O'Cearbhaill, Karen A. Cadoo, Jacqueline Gallagher, Sara Kravetz, Autumn McDonnell, Tiffany Troso-Sandoval, Paul Sabbatini, Stuart Lichtman, William Tew, Vicky Makker, Rachel N. Grisham, David M. Hyman, Carol Aghajanian, Jason Konner. A PHASE 2 STUDY OF TPIV200/HUFR-1 (A MULTI-EPITOPE FOLATE RECEPTOR ALPHA VACCINE) IN COMBINATION WITH DURVALUMAB IN PATIENTS WITH PLATINUM RESISTANT OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr AP27.