Exploratory efficacy and translational results from the safety run in of AHEAD-MERIT, a phase II trial of first line pembrolizumab plus the fixed-antigen cancer vaccine BNT113 in advanced HPV16+ HNSCC

BackgroundThe safety run in cohort of the ongoing AHEAD-MERIT phase II trial confirmed the tolerability of BNT113, an investigational uridine mRNA-lipoplex (LPX) cancer vaccine encoding HPV16 E6 and E7 oncoproteins, in combination with pembrolizumab (ESMO-IO 2022 #155P). We present efficacy, biomarker, and updated safety data.MethodsBNT113-01 is an open-label, multi-site, phase II trial of BNT113 (8xq1w, then q3w) + pembrolizumab (200 mg q3w) vs pembrolizumab monotherapy as first line treatment in pts with unresectable recurrent or metastatic HPV16+ PD-L1+ HNSCC. The non-randomized safety run in phase assessed the combination in 15 pts, with safety and tolerability as primary and efficacy as secondary endpoint. Biomarker analyses included cytokine profile, HPV16 and PD-L1 status, plus cellular responses (ELISpot, Multimer, TCRseq) in 3 pts.ResultsAs of 15 DEC 2023, 15 male safety run in pts (median age 66, range 41 – 74 years) have received BNT113 + pembrolizumab (median exposure 7.0 [1.6 – 18.2] months). Responses assessed by central blinded independent review after 12 months median follow up occurred in 6/15 pts, with 4 complete and 2 partial responses (unconfirmed overall response rate 40%), plus 2 stable disease (disease control rate 53%). Median progression free survival (PFS) was 3.9 [95% CI: 2.1, 12.9] months, with estimated 6 and 12 month PFS of 42% and 28%, respectively. Median overall survival was 22.6 [11.8, NE] months. Safety data was in line with prior published results. TEAEs occurred in all pts; TEAEs related to BNT113 were mainly Grade 1-3 flu-like symptoms. Grade ≥3 AEs related to BNT113 (anemia, pyrexia, decreased appetite) and pembrolizumab occurred in 2 pts each, related TESAEs in 2 and 3 pts, respectively, with no treatment-related deaths. 2/3 pts assessed showed de novo vaccine-induced T-cell responses against E6 and E7 oncoproteins, with HPV16E7-specific CD8 T cells reaching 5.2% of peripheral CD8+ T cells after 10 months in a pt with prolonged stable disease.ConclusionsBNT113 + pembrolizumab was well tolerated, showed encouraging signs of efficacy, and the RP2D was confirmed. We will present serum cytokine and T cell profiling data.Clinical trial identificationNCT04534205.Editorial acknowledgementThe authors would like to acknowledge Andrew Finlayson (of BioNTech) for medical writing support.Legal entity responsible for the studyBioNTech SE.FundingBioNTech SE.DisclosureN.F. Saba: Financial Interests, Personal, Advisory Board, advisory compensated or non compensated role: AstraZeneca Eisai Medical Exelixis Merck Merck EMD Serono, Pfizer, Kura, Vaccinex, CUE, BionTech; Financial Interests, Personal, Advisory Board, Advisory compensated or non-compensated role: GSK, TOSK, Seagen, Flamingo, Infinity, Inovio, Aveo, Medscape, Onclive, Uptodate, BMS, Fulgent Springer, Nanobiotix, Taiho; Financial Interests, Personal, Advisory Board, Advisroy compensated or non-compensated role: Cornerstone, Celldex, Surface Oncology Astex, Imugene, Faron Pharmaceutical, Coherus, Adagene; Financial Interests, Personal, Royalties, I receive compensation or royalties: Uptodate, Springer; Financial Interests, Institutional, Coordinating PI, Agreement with institution or with me personally: EMD Serono, Exelixis, Biontech, AstraZeneca; Non-Financial Interests, Leadership Role, Emory University: Vice Chair, Hematology and Medical Oncology. K. Klinghammer: Financial Interests, Personal, Advisory Board: BMS, MSD; Financial Interests, Personal, Invited Speaker: Merck Sanofi, Onkowissen, Biontech; Non-Financial Interests, Principal Investigator: AstraZeneca, GSK, Kura Oncol, MSD, Biontech; Non-Financial Interests, Advisory Board: DGHO, DKG, AIO. A.D. Colevas: Financial Interests, Institutional, Local PI: BioNTech; Financial Interests, Institutional, Sponsor/Funding: BioNTech. T. Rutkowski: Financial Interests, Institutional, Local PI: BioNTech SE. D. Thurner, U. Müller-Richter: Financial Interests, Institutional, Local PI: BioNTech; Financial Interests, Institutional, Sponsor/Funding: BioNTech. M. Maio: Financial Interests, Personal, Advisory Board: BMS, Roche, GSK, Sanofi, Alfasigma, Amgen, Sciclone, Eli Lilly, MSD, Incyte, Pierre Fabre, AstraZeneca, Pfizer, Merck Serono; Financial Interests, Personal, Stocks/Shares: Epigen, Theravance. J.S. Grewal: Financial Interests, Institutional, Local PI: BioNTech; Financial Interests, Institutional, Sponsor/Funding: BioNTech. C.H.H. Ottensmeier: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Roche Genentech; Financial Interests, Personal, Other, consulting: Sebastian Bio; Financial Interests, Personal, Other, head of SAB: Neuvogen; Financial Interests, Personal, Stocks/Shares: Neuvogen; Financial Interests, Institutional, Research Grant, trial funding: Verastem, Merck Sharpe and Dohme; Financial Interests, Institutional, Coordinating PI, phase I trial: Transgene; Financial Interests, Institutional, Coordinating PI: Delcath Systems, PsiOxus, Touchlight genetics; Financial Interests, Coordinating PI, Coordinating PI on two clinical trials: Biontech; Financial Interests, Institutional, Research Grant, trial funding to previous employer (HARE40 trial): Biontech. J. Dias, H. Yang, R. Das, J. Furlanetto, A. Herzfeldt, M. Kühnle, A. Ulges, J. Alles: Financial Interests, Personal, Full or part-time Employment: BioNTech; Financial Interests, Personal, Stocks/Shares: BioNTech. Ö. Türeci: Financial Interests, Personal, Full or part-time Employment: BioNTech; Financial Interests, Personal, Leadership Role: BioNTech; Financial Interests, Personal, Member of Board of Directors: BioNTech; Financial Interests, Personal, Stocks or ownership: BioNTech. U. Sahin: Financial Interests, Personal, Full or part-time Employment: BioNTech; Financial Interests, Personal, Leadership Role: BioNTech; Financial Interests, Personal, Member of Board of Directors: BioNTech; Financial Interests, Personal, Stocks or ownership: BioNTech. All other authors have declared no conflicts of interest.