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Clinical Trial
. 2024 Oct:189:90-97.
doi: 10.1016/j.ygyno.2024.07.675. Epub 2024 Jul 27.

Vaccination with folate receptor-alpha peptides in patients with ovarian cancer following response to platinum-based therapy: A randomized, multicenter clinical trial

Aditi Gupta  1 , Roisin E O'Cearbhaill  2 , Matthew S Block  3 , Erika Hamilton  4 , Jason A Konner  2 , Keith L Knutson  5 , James Potts  6 , Gerald Garrett  7 , Richard T Kenney  7 , Robert M Wenham  8 ; TPIV200 Ovarian Cancer Study Investigators (listed at the end)
Affiliations
Clinical Trial

Vaccination with folate receptor-alpha peptides in patients with ovarian cancer following response to platinum-based therapy: A randomized, multicenter clinical trial

Aditi Gupta et al. Gynecol Oncol. 2024 Oct.

Abstract

Objective: Folate receptor alpha (FRα) is overexpressed on >90% of high-grade epithelial ovarian cancers (EOC). Targeting FRα with antibody-drug conjugates has proven utility in the platinum-resistant setting. It is also a potential therapeutic target for immuno-oncologic agents, such as peptide vaccines that work primarily via adaptive and humoral immunity. We tested the hypothesis that FRα peptide immunization could improve outcomes in patients with EOC following response to platinum-based therapy.

Methods: We conducted a randomized, double-blind, multicenter, phase II study to evaluate the safety and efficacy of TPIV200 (a multi-epitope FRα peptide vaccine admixed with GM-CSF) versus GM-CSF alone in 120 women who did not have disease progression after at least 4 cycles of first-line platinum-based therapy. Patients were vaccinated intradermally once every 4 weeks up to 6 times, followed by a boosting period of 6 vaccinations at 12-week intervals. Primary endpoints included safety, tolerability, and progression free survival (PFS).

Results: At study termination with a median follow-up of 15.2 months (range 1.2-28.4 months), 68 of 119 intention-to-treat patients had disease progression (55% in TPIV200 + GM-CSF arm and 59% in GM-CSF alone arm). The median PFS was 11.1 months (95% CI 8.3-16.6 months) with no significant difference between the treatment groups (10.9 months with TPIV200 + GM-CSF versus 11.1 months with GM-CSF, HR, 0.85; upper 90% CI 1.17]. No patient experienced a ≥ grade 3 drug-related adverse event.

Conclusion: TPIV200 was well tolerated but was not associated with improved PFS. Additional studies are required to uncover potential synergies using multiepitope vaccines targeting FRα. Trial Registration NLM/NCBI Registry, NCT02978222, https://clinicaltrials.gov/search?term=NCT02978222.

Keywords: Folate receptor alpha; GM-CSF; Multi-epitope vaccine; Ovarian cancer.

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Conflict of interest statement

Conflicts of interest KK is listed as a coinventor on a patent entitled ‘Immunity to folate receptors’, which is owned by the Mayo Clinic and was previously licensed to Marker Therapeutics. KK reports receiving commercial research support from Marker Therapeutics. REO reports institutional research grants from ArsenalBio, AstraZeneca/Merck, Atara Biotherapeutics/Bayer, Genentech, Genmab, GSK, Gynecologic Oncology Group Foundation, Juno Therapeutics, Kite/Gilead, Ludwig Institute for Cancer Research, Lyell Therapeutics, Marker Therapeutics, OnCusp Therapeutics, Regeneron, Sellas Life Sciences, Stemcentrx, Syndax, TapImmune, and TCR2 Therapeutics; participating in advisory boards with Bayer, Carina Biotech, Immunogen, Miltenyi, Loxo, Regeneron, R-Pharm, Seattle Genetics, and Tesaro/GSK; personal fees from GOG Foundation; travel fees from Hitech Health. RMW reports grants or funding from Anixa Biosciences, Merck, OnTarget; consulting, DSMB, or advisory fees from Eisai, Sonnet Biotherapeutics, Genentech, Abbvie, Shattuck Labs, Merck, GSK/Tesaro, Legend Biotech, Novocure, Clovis, AstraZeneca, Regeneron, Mersana, Seagen; travel support from Eisai, Tapimmune/Marker Therapeutics; speakers bureau fees from GSK, CurioScience, Onclive; stock from Ovation Diagnostics. MSB is listed as a coinventor on pending patents entitled, “Combinations of Dendritic Cell-Based Vaccines” and “Checkpoint Inhibitors and Dendritic Cell-Based Vaccines and Uses Thereof;” reports institutional research support from Alkermes, Bristol-Myers Squibb, Genentech, Marker Therapeutics, Merck, nFerence, Pharmacyclics, Regeneron, Sorrento, TILT Biotherapeutics, Transgene, and Viewpoint Molecular Therapeutics; and is has served as a consultant/SAB member for Marker Therapeutics, Sorrento Therapeutics, TILT Biotherapeutics, and Viewpoint Molecular Targeting.

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