941TiP - A phase I/IIa, open-label, dose-finding trial to evaluate safety, immunogenicity, and anti-tumour activity of VB10.16 in combination with pembrolizumab in patients with unresectable recurrent or metastatic HPV16-positive head and neck squamous cell carcinoma (R/M HNSCC)

Background

In the US and UK, Human Papilloma Virus (HPV) causes 71% and 52% of Oropharyngeal Squamous Cell Carcinoma (OPSCC), predominantly HPV 16-induced. At least 10-25% of patients diagnosed with OPSCC develop recurrence within 2 years after initial therapy. Standard treatment for R/M HNSCC is pembrolizumab +/- chemotherapy. However, the treatment response to pembrolizumab alone is limited (19% response rate). The HPV oncogenes E6 and E7 are ideal targets for therapeutic HPV vaccines. VB10.16, a DNA-based vaccine encoding E6 and E7 proteins from HPV16 linked to natural human chemokine (CC motif) ligand 3-like 1 (CCL3L1), triggers strong HPV-specific T-cell responses. After VB10.16 monotherapy in patients with HPV16-positive high-grade cervical intraepithelial neoplasia, a PD-L1 upregulation post-vaccination has been observed indicating that VB10.16 may sensitize tumours to anti-PD(L) 1 treatment. In a Phase II trial in R/M cervical cancer, VB10.16 combined with atezolizumab showed a favourable safety profile and promising efficacy. Boosting T-cell responses with VB10.16 could be a valuable strategy to improve outcomes in HPV16-positive R/M OPSCC patients.

Trial design

This phase I/IIa, open-label, dose-finding trial is designed to evaluate safety, tolerability, immunogenicity with HPV16 E6/E7 specific cellular immune responses, and anti-tumour activity of VB10.16 in patients with HPV16-positive R/M HNSCC whose tumours express PD-L1 (CPS ≥ 1) and who are eligible for pembrolizumab monotherapy. The trial is designed to determine the biological optimal dose of VB10.16 in combination with a fixed dose of pembrolizumab based on the totality of data. The trial consists of 2 phases with: a dose escalation phase (phase I) and a dose expansion phase (phase IIa). After 48 weeks of combination treatment, patients can either continue pembrolizumab with 200 mg Q3W administration or change to 400 mg Q6W at the discretion of the investigator and after consultation with the Sponsor corresponding to approximately 2 years of treatment. Pembrolizumab is supplied by MSD.

Clinical trial identification

EudraCT 2022-002029-81 EU Trial Number: 2022-503055-26-00 Approval UK 22JUN2023 Approval CTIS (Protocol) 30Aug2023 NCT06016920.

Editorial acknowledgement

Legal entity responsible for the study

Nykode Therapeutics ASA.

Funding

Nykode Therapeutics ASA.

Disclosure

S. Khalique: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Advisory Role: Grey Cell Research. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pfizer, Novartis, Takeda, MSD, Bristol Myers Squibb, Bayer; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Coordinating PI: Roche, AstraZeneca; Financial Interests, Personal and Institutional, Local PI: MSD, Amgen, Celon Pharma, Pfizer, Novartis, Brsitol Myers Squibb, Eli Lilly, Loxo; Financial Interests, Personal and Institutional, Other, Subinvestigator and ad hoc Consultant: PDC* line Pharma; Financial Interests, Local PI: OSE Immunotherapeutics; Non-Financial Interests, Institutional, Product Samples: Novartis, Pfizer, AstraZeneca, Roche. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Coordinating PI: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. B. Melichar: Financial Interests, Personal, Advisory Board: MSD, Merck. T. Rutkowski: Financial Interests, Personal, Invited Speaker: MSD, Roche, Merck, BMS. M. Guix Arnau: Financial Interests, Personal, Invited Speaker: BMS, Astellas, Merck, Sanofi, Roche, Kyowa-Kirin, MSD. T. Jürgens: Financial Interests, Institutional, Full or part-time Employment: Nykode Therapeutics; Financial Interests, Personal, Stocks/Shares: Nykode Therapeutics. All other authors have declared no conflicts of interest.