Cemiplimab plus peltopepimut-S vaccine in recurrent cervical cancer: A phase 2 clinical trial
- PMID: 40154184
- DOI: 10.1016/j.ygyno.2025.03.019
Cemiplimab plus peltopepimut-S vaccine in recurrent cervical cancer: A phase 2 clinical trial
Abstract
Objective: To estimate the clinical benefit of cemiplimab+peltopepimut-S vaccine after disease progression on first-line chemotherapy.
Methods: This global phase 2 open-label study (NCT04646005) recruited patients with recurrent HPV16+ cervical cancer who had previously experienced disease progression after first-line chemotherapy. Patients received a total of 3 doses of peltopepimut-S vaccine on days 1, 29, and 50 and cemiplimab 350 mg every 3 weeks until disease progression or other reason for early discontinuation. Primary endpoint was objective response rate (ORR) per RECIST version 1.1; secondary endpoints were duration of response (DOR), overall survival (OS), progression-free survival (PFS), and safety.
Results: Of 113 patients enrolled between June 28, 2021 and May 22, 2023, 80.5 % were white, with a median age of 49.0 years, and 58.4 % had an ECOG PS of 0. Median duration of follow-up was 4.9 months. ORR (95 % CI) per investigator assessment was 16.8 % (9.9-23.7). ORR of patients with squamous cell carcinoma by PD-L1 expression in tumor cells was 15.8 % for patients with PD-L1 < 1 % and 24.1 % for patients with PD-L1 ≥ 1 %. Median (95 % CI) DOR was 5.6 (3.5-not estimable) months. Median (95 % CI) OS and PFS were 13.3 (10.8-16.3) months and 3.0 (1.7-4.0) months, respectively. Treatment-emergent adverse events (TEAEs) occurred in 92.9 % of patients, the most common being injection-site reaction (38.9 %) and anemia (25.7 %). Six (5.3 %) patients died from a TEAE.
Conclusion: Cemiplimab+peltopepimut-S vaccine provides similar benefits to cemiplimab monotherapy; patients with higher PD-L1 expression in tumor cells may be more likely to benefit from treatment.
Keywords: Cemiplimab; Cervical cancer; HPV16; Peltopepimut-S vaccine; Recurrent/metastatic.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest Domenica Lorusso: honoraria from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, PharmaMar, Seagen, and Sutro; consulting or advisor role for AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvent, PharmaMar, Seagen, and Sutro; speakers bureau for AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, PharmaMar, and Seagen; research funding from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, PharmaMar, Roche, and Seagen; principal investigator of trials for AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, PharmaMar, Roche, and Seagen; member of the GCIG Board of Directors and the MITO Board of Directors; and grants for travelling from AstraZeneca, Clovis Oncology, and GSK. Ana Oaknin: personal fees for advisory board membership from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Daiichi Sankyo, Debiopharm International, Deciphera Pharmaceuticals, Eisai, Exelisis, EMD Serono, F. Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, Merck Sharp & Dohme de España, SA, Mersana Therapeutics, Myriad Genetics, Novocure, OneXerna Therapeutics, Inc., PharmaMar, Regeneron Pharmaceuticals, Inc., Sattucklabs, Seagen, Sutro Biopharma, and Zentalis; personal fees for travel/accommodation from AstraZeneca, PharmaMar, and Roche; non-remunerated roles at ESMO (member, Officer, Co-Chair of the ESMO Gynaecological Cancers Congress 2023–2025, Chair of the Gynaecological Track ESMO 2019, Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022, member of the Gynaecological Cancers Faculty and Subject Editor for the Gynaecological Clinical Practice Guidelines); a non-remunerated role at GCIG (member and Cervix Cancer Chair on behalf of GEICO); and European Society of Gynaecological Oncology (ESGO) Council Member and membership of ASCO, GOG, and SEOM. Giuliano Santos Borges: no conflict of interest. Fernanda Damian: no conflict of interest. Nelleke Ottevanger: no conflict of interest. Toon Van Gorp: consulting or advisory role (all payments to institution) for AstraZeneca, Immunogen, Eisai, OncXerna Therapeutics, GSK, MSD/Merck, Seagen, Tubulis GmbH, Incyte, Zentalis, Karyopharm Therapeutics, and BioNTech SE; speakers' bureau (all payments to institution) for GSK, MSD/Merck, and ImmunoGen; research funding (all payments to institution) from Amgen, Roche, and AstraZeneca; and travel, accommodation, and expenses from MSD/Merck, Immunogen, GSK, PharmaMar, and AstraZeneca. Carlos Eduardo Paiva: no conflict of interest. Judith Kroep: consulting or advisory role (all payments to institution) for AstraZeneca, Eisai, GSK, Immagene, Lilly, and MSD/MERCK; research funding (all payments to institution) from AstraZeneca, Novartis, and Philips/Innosign; and travel and accommodation from Daiichi Sankyo. Yong-Man Kim: research funding from MSD, AstraZeneca, Roche, Genmab, Canaria Bio, Seagen, and BeiGene; and a speaker role for Chugai. Hee Seung Kim: no conflict of interest. Jae Kwan Lee: no conflict of interest. Hannelore Denys: consulting or advisory roles for Pfizer, Roche, PharmaMar, AstraZeneca, Eli Lilly and Company, Novartis, Amgen, GSK, MSD, Seagen, Gilead Sciences, and Teva; research funding to institution from Gilead; and travel, accommodation, and expenses from Pfizer, Roche, PharmaMar, Teva, AstraZeneca, Gilead Sciences, MSD Oncology, and GSK. Roy Lalisang: no conflict of interest. Andreia Cristina De Melo: grants or contracts from Amgen, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, GSK, MSD, Novartis, Pierre Fabre, Regeneron Pharmaceuticals, Inc., and Roche, with payments made to the institution; and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Adium, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, GSK, MSD, Novartis, and Roche. Andres Redondo: consulting or advisory roles for AstraZeneca, GSK, Boehringer Ingelheim, MSD, and Pharma&; speakers bureau for AstraZeneca, GSK, MSD, and Pharma&; and travel, accommodation, and expenses from AstraZeneca. Anna KL Reyners: no conflict of interest. Paulo Mora: personal fees for advisory boards from AstraZeneca and Knight; travel and accommodation from AstraZeneca; and research funding to institution from AstraZeneca and Regeneron Pharmaceuticals, Inc. Celine Closset: no conflict of interest. Cornelis JM Melief: employee and beneficiary of stock appreciation rights in ISA Pharmaceuticals. Leon Hooftman: employee and stock option holder of ISA Pharmaceuticals. Shaheda Jamil, Lisa Boersma, Suk-Young Yoo, Matthew G Fury, Melissa Mathias, Frank Seebach, and Israel Lowy: employees and shareholders of Regeneron Pharmaceuticals, Inc. Nicoletta Colombo: consulting or advisory roles with Roche/Genentech, AstraZeneca, Clovis Oncology, MSD Oncology, GSK, Immunogen, Mersana, Eisai, Nuvation Bio, OncXerna, Pieris Pharmaceuticals, and Novocure; speakers' bureau for AstraZeneca, Clovis Oncology, GSK, MSD Oncology, and Eisai; travel, accommodation, and expenses from GSK, AstraZeneca, and Corcept Therapeutics; honoraria from Roche/Genentech, AstraZeneca, GSK, MSD Oncology, Clovis Oncology, Immunogen, Mersana, Eisai, Nuvation Bio, OncXerna, Pieris Pharmaceuticals, and Novocure; research funding from AstraZeneca, Roche, and GSK; and employment of an immediate family member at Sarepta Therapeutics.
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