877P - 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

Background

The 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.

Methods

BNT113-01 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.

Results

As 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.

Conclusions

BNT113 + 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 identification

NCT04534205.

Editorial acknowledgement

The authors would like to acknowledge Andrew Finlayson (of BioNTech) for medical writing support.

Legal entity responsible for the study

BioNTech SE.

Funding

BioNTech SE.

Disclosure

N.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.