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Objective: This study aimed to evaluate the utility of serum cancer antigen-125 (CA-125) levels to monitor patients with epithelial ovarian cancer (EOC) undergoing immune checkpoint inhibitor (ICI) therapy., Method: This was a single-center retrospective review of all patients with EOC who were treated with ICI therapy from January 2013 to May 2017. This study compared the percentage change in baseline CA-125 in patients who had clinical benefit, defined as complete response, partial response, or stable disease by RECIST 1.1, with duration ≥24 weeks, versus those who did not. The groups were compared by Wilcoxon rank-sum test., Results: Fifty-nine (66%) of 89 patients who underwent ICI therapy had CA-125 data at baseline and during treatment. Of those who derived clinical benefit, 11/15 (73%) experienced an increase in CA-125 from baseline to end of treatment. Of those who did not derive clinical benefit, 36/44 (82%) experienced a CA-125 increase (p = 0.48). The average % increase from baseline to within 12 weeks of treatment initiation for patients with and without clinical benefit was 34% and 195%, respectively (p = 0.008)., Conclusion: Our analysis demonstrates a statistically significant difference in the magnitude of increase in CA-125 levels within the first 12 weeks of treatment between patients who achieved clinical benefit and those who did not. However, both groups of patients were equally likely to experience an increase in CA-125 within 12 weeks. These findings suggest that physicians should apply caution when using early CA-125 data to guide treatment decisions for patients with EOC undergoing ICI therapy., Competing Interests: Declaration of competing interest Outside the submitted work: Dr. Zamarin reports personal fees from Merck, Agenus, Hookipa Biotech, and Western Oncolytics, grants from Merck, sponsored trave from Genentech, and stock options from Calidi Biotherapeutics. Dr. Konner reports personal fees from Astra-Zeneca, Inc. Dr. Callahan reports grants, as well as “other” (family member is an employee) from Bristol Myers Squibb, and personal fees from Merck, InCyte, Moderna, and AstraZeneca. Dr. Cadoo reports travel/expenses and institutional support from AstraZeneca, institutional support from Syndax Pharmaceuticals, as well as personal fees and travel/expenses from Tessaro and personal fees from OncLive. Dr. Friedman reports steering committee (compensation waived, research financial support to institution) from Genentech and Merck, institutional support from Bristol Myers Squibb, and personal fees from AstraZeneca. Dr. O'Cearbhaill reports personal fees from Tesaro, GlaxoSmithKline, and Clovis, and she is a non-compensated steering committee member for the PRIMA (niraparib) study and DUO-O (olaparib) study. Dr. Aghajanian reports personal fees from Tesaro, Immunogen, Clovis, Mateon Therapeutics, Eisai/Merck, Mersana Therapeutics, and Roche, as well as grants from Clovis, grants from Genentech, AbbVie, and AstraZeneca. Dr. Sabbatini reports institutional support from Bristol Myers Squibb. Dr. Iasonos reports personal fees from Intelligencia, Mylan, and Brightpath., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Immune checkpoint inhibitors (ICIs) to date have demonstrated limited activity in advanced ovarian cancer (OC). Folate receptor alpha (FRα) is overexpressed in the majority of OCs and presents an attractive target for a combination immunotherapy to potentially overcome resistance to ICI in OCs. The current study sought to examine clinical and immunologic responses to TPIV200, a multiepitope FRα vaccine administered with programmed death ligand 1 (PD-L1) inhibitor durvalumab in patients with advanced platinum-resistant OC., Methods: Following Simon two-stage phase II trial design, 27 patients were enrolled. Treatment was administered in 28-day cycles (intradermal TPIV200 and granulocyte-macrophage colony-stimulating factor (GM-CSF) for 6 cycles and intravenous durvalumab for 12 cycles). Primary endpoints included overall response rate and progression-free survival at 24 weeks. Translational parameters focused on tumor microenvironment, PD-L1 and FRα expression, and peripheral vaccine-specific immune responses., Results: Treatment was well tolerated, with related grade 3 toxicity rate of 18.5%. Increased T cell responses to the majority of peptides were observed in all patients at 6 weeks (p<0.0001). There was one unconfirmed partial response (3.7%) and nine patients had stable disease (33.3%). Clinical benefit was not associated with baseline FRα or PD-L1 expression. One patient with prolonged clinical benefit demonstrated loss of FRα expression and upregulation of PD-L1 in a progressing lesion. Despite the low overall response rate, the median overall survival was 21 months (13.5-∞), with evidence of benefit from postimmunotherapy regimens., Conclusions: Combination of TPIV200 and durvalumab was safe and elicited robust FRα-specific T cell responses in all patients. Unexpectedly durable survival in this heavily pretreated population highlights the need to investigate the impact of FRα vaccination on the OC biology post-treatment., Competing Interests: Competing interests: KK is listed as a coinventor on a patent entitled 'Immunity to folate receptors', which is owned by the Mayo Clinic and licensed to Marker Therapeutics. MB and KK report receiving commercial research support from Marker Therapeutics. DZ reports personal/consultancy fees from Merck, Synlogic Therapeutics, Biomed Valley Discoveries, Trieza Therapeutics, Tesaro, and Agenus, outside of the scope of the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)