878P - Final results of a phase II study of peltopepimut-S and cemiplimab in patients with relapsed/metastatic HPV16+ oropharyngeal cancer that progressed with prior anti-PD-1 therapy

Background

Peltopepimut-S (ISA101b) is a synthetic long peptides-based therapeutic vaccine targeting the human papillomavirus type 16 (HPV16) that induces specific expansion of both CD4+ helper and CD8+ cytotoxic T-cells against HPV16 E6/E7 oncoproteins. Having previously reported stage 1 data (A. Kong, et al. J Clin Oncol 2023;41:suppl.6028), we present the final results of this phase II trial of patients with relapsed/metastatic (R/M) HPV16+ oropharyngeal cancer (OPC) that had progressive disease (PD) within 6 months after prior 1^st or 2^nd line anti-PD-1 therapy.

Methods

In this single-arm phase II study, patients were treated with peltopepimut-S (subcutaneously 100μg/peptide) following a 3-dose schedule (Days 1, 29 and 50) plus cemiplimab (intravenously 350mg as a 3-weekly regimen) until PD. Patients still on study after 6 months were offered one peltopepimut booster injection. HPV16 positive tumor status was centrally confirmed using a PCR assay. The primary efficacy endpoint was overall response rate (ORR) as per RECIST 1.1.

Results

Sixty-four patients (mean age 61.5 ± 10.6 years; 57 [89.1%] male) were included in the efficacy analysis. The median follow-up was 40.9 weeks (range 1.6-138.7). The overall response rate (ORR) was 6.3% (four tumor responses, all partial [PR]). The clinical benefit rate (CBR, consisting of PR and stable disease) was 56.3% (36 patients). Eighteen patients (28.1%) received the booster injection. Median overall survival (OS) was 11.3 months (range 0.3-29.7), and median progression-free survival (PFS) was 3.6 months (95% CI:1.8-4.7). Two grade 3 adverse events (AEs) related to peltopepimut-S occurred: erythema at the injection site and diarrhea. Three patients (4.7%) had grade 3 immunotoxicity: diarrhea, gastritis and pneumonitis. Grade 4-5 AEs related to study treatment did not occur.

Conclusions

The combination of peltopepimut-S and cemiplimab was well tolerated, and resulted a CBR of 56.3% and mOS of 11.3 months in patients with relapsed/metastatic HPV16+ oropharyngeal cancer that progressed on or soon after anti-PD1 therapy.

Clinical trial identification

2020-003652-32.

Editorial acknowledgement

Legal entity responsible for the study

ISA Therapeutics B.V.

Funding

Regeneron Pharmaceuticals, Inc.

Disclosure

A. Kong: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Mad, Bristol Myers Squibb, Merck; Financial Interests, Personal, Other, consultant for a project: MSD; Financial Interests, Personal, Other, adviser or consultant: Avvinity Therapeutics; Financial Interests, Funding, PUMA previously funded a research project which has ended in 2022: PUMA therapeutics; Financial Interests, Institutional, Funding: AstraZeneca. C. Even: Financial Interests, Personal, Advisory Board: BMS, MSD, Innate Pharma, Merck Serono; Financial Interests, Institutional, Advisory Board: F Star Therapeutics, Novartis, Elevar, Bicara, PDS Biotechnology, GSK, Merus; Financial Interests, Institutional, Local PI: BMS, AstraZeneca, ISA pharmaceutics, MSD, Debiopharma, Ayala, Gilead, GSK, Beigene, Takeda, Genmab, Seagen, Nykode; Financial Interests, Institutional, Coordinating PI: BMS, Novartis, Sanofi. B. Aguilera: Financial Interests, Institutional, Full or part-time Employment, Clinical Project Manager: ISA Pharmaceuticals BV; Financial Interests, Personal, Stocks/Shares, Stock Appreciation Rights: ISA Pharmaceuticals BV. M. Klein Hesselink: Financial Interests, Personal, Full or part-time Employment, Until 30 April 2024: ISA Pharmaceuticals; Financial Interests, Personal, Full or part-time Employment, As of 1 May 2024: TargED Biopharmaceuticals BV; Financial Interests, Personal, Stocks/Shares: TargED Biopharmaceuticals BV. S. Visscher: Financial Interests, Personal, Full or part-time Employment: ISA Pharmaceuticals B.V. C.H. Chung: Financial Interests, Personal, Advisory Board, Scientific Advisory board participation: Fulgent, Genmab, AVEO, Seagen, Regeneron, Exelixis; Financial Interests, Institutional, Local PI, Clinical trial participation: Seagen, Bicara, ALX, CUE, ISA. J.C. Park: Financial Interests, Institutional, Local PI: Inhibrx, Ankyra, ALX, A2 Bio, CUE Bio, Alentis. D.R. Adkins: Financial Interests, Personal, Advisory Board: Merck, Cue Biopharma, Kura, Vaccinex, Xilio, Targimmune, Immunitas, Adlai Nortye, EMD Serono, Genmab, Jazz Therapeutics, Merck KGAA, Merus, Purple Biotech, Regeneron, Seagen, Boehringer Ingelheim, Eisai Europe, Inhibrx; Financial Interests, Personal, Other, Safety Review: Gilead Sciences; Financial Interests, Institutional, Local PI: ISA, Pfizer, Eli Lilly, Celgene/BMS, Novartis, AstraZeneca, Blueprint Medicine, Kura, Exelixis, Innate, Cue biopharma, Debiopharm, Epizyme, Hookipa, Roche, Merus, Gilead Sciences, Beigene, Vaccinex, Adlai Nortye, Bioatla, Calliditas, Natco, Immutep, Tizona, Genmab, Boehringer Ingelheim, Xilio, Alentis, Coherus, Inhibrx, Seagen, GSK, Daiichi Sankyo, Janux, Johnson & Johnson, Tempus; Financial Interests, Institutional, Coordinating PI: Merck; Financial Interests, Institutional, Research Grant: CoFactor; Non-Financial Interests, Other, Member of the NCCN Head and Neck Panel: NCCN. K.J. Harrington: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Merck, MSD, Pfizer, Replimune, Oncolys, Vyriad, Idera; Financial Interests, Institutional, Other, Honoraria for lectures: Amgen, AstraZeneca, BMS, Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board, Advisory board for CD47 assets: Arch Oncology; Financial Interests, Institutional, Advisory Board, Development of DDR assets: ARTIOS; Financial Interests, Institutional, Advisory Board, Development of exosomal STING agonist: Codiak; Financial Interests, Institutional, Advisory Board, Development of oncolytic adenovirus: PsiVac; Financial Interests, Institutional, Funding, Research: AstraZeneca, Boehringer Ingelheim, MSD; Financial Interests, Institutional, Funding, Development of oncolytic HSV platform: Replimune; Non-Financial Interests, Leadership Role, Chair of Steering Committee: ART NET; Non-Financial Interests, Other, Member of Global Steering Committee: MR - Linac. J. Fayette: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Innate Pharma, Merck Serono, Roche, Pfizer, Hookipa; Non-Financial Interests, Principal Investigator: AstraZeneca, MSD, Pfizer, Meru, Calliditas, Isa. S. Rottey: Financial Interests, Institutional, Advisory Board: Pfizer, Merck, Roche, Ipsen, BMS; Financial Interests, Institutional, Invited Speaker: Ipsen, BMS, Astellas; Financial Interests, Institutional, Research Grant: MSD, Roche, BMS; Non-Financial Interests, Principal Investigator, It is my main task in the hospital to attract and perform clinical trials in oncology phase I-III: all companies performing clinical trials in oncology in Europe. A. Algazi: Financial Interests, Personal, Other, Advisor, SAB member: Onchilles, Sensei; Financial Interests, Personal, Other, DSMB Member: Worldwide Clinical Trials; Financial Interests, Personal, Other, Advisor: Bluesphere; Financial Interests, Personal, Invited Speaker: Asher, Ascendis; Financial Interests, Personal, Stocks/Shares: Onchilles, Sensei, Valitor; Financial Interests, Institutional, Local PI, Clinical trial funding to UCSF: Asher, Ascendis, Pfizer, Vaccinex, Incyte; Financial Interests, Institutional, Coordinating PI, Clinical trial funding to UCSF: Genentech. M.G. Fury: Financial Interests, Personal, Full or part-time Employment, I am a full time employee: Regeneron Pharmaceuticals; Financial Interests, Personal, Stocks/Shares, I hold employee stock: Regeneron Pharmaceuticals; Other, My wife is also a full time employee at Regeneron, and holds employee stock: Regeneron Pharmaceuticals. C.J.M. Melief: Financial Interests, Institutional, Full or part-time Employment, I am Chief Scientific Officer of ISA Pharmaceuticals: ISA Pharmaceuticals; Financial Interests, Personal, Stocks/Shares, I have shares in this company and stock appreciation rights: ISA Pharmaceuticals. L.W. Hooftman: Financial Interests, Institutional, Full or part-time Employment, Chief Medical Officer of the company: ISA Pharmaceuticals BV; Financial Interests, Personal, Stocks/Shares, Share Options: ISA Pharmaceuticals BV. All other authors have declared no conflicts of interest.