870P - POPPY: A phase II trial to assess the efficacy and safety profile of pembrolizumab in patients of performance status 2 with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC)

Background

Pembrolizumab, with or without chemotherapy is a standard treatment for fit patients with R/M HNSCC, with median survival of 8-11 months. Pembrolizumab alone has a response rate of ∼15% in PD-L1 unselected patients. However, many patients with R/M HNSCC are not fit and there is no accepted standard of care these patients, who have a median survival of 3-6 months with best supportive care alone.

Methods

POPPY (NCT03813836) is a UK multicentre single-arm phase II trial in patients with R/M HNSCC and a WHO Performance Status (PS) of 2. Patients receive pembrolizumab 200 mg intravenously every 3 weeks, for up to 24 months. Primary endpoint is disease control rate (DCR) at 24 weeks, using iRECIST. 59 patients are required to detect a disease control rate (DCR) ≥20% and exclude an unacceptable DCR ≤10%, with 85% power and one-sided 15% significance level. Secondary endpoints include toxicity, response, progression-free survival (PFS) and overall survival (OS). Blood and tissue are collected for exploratory translational studies.

Results

63 patients were recruited from 12 UK centres (Aug 2019 – Aug 2023). 57 patients received pembrolizumab, median 4.5 cycles (range: 1-32). Treatment-related adverse events were observed in 31 (54.4%), with grade 3 or higher events seen in 9 patients (15.8%; 1 grade 4 colitis, no grade 5 events). 54 patients were eligible and evaluable for disease response. DCR at 24 weeks was 27.8% (95%CI:16.5-41.6), exceeding the unacceptable DCR rate of 10%. The overall response rate was 31.5% (17/54; 95%CI:19.5-45.6), with a median PFS of 4.0 (95%CI:2.1-5.7) and OS of 7.6 (95%CI:6.7-10.6) months respectively.

Conclusions

POPPY is the first prospective study to evaluate pembrolizumab in PS2 patients with R/M HNSCC. It demonstrates meaningful anti-tumor activity, with no signals of increased toxicity; this is particularly encouraging as the observed results are consistent with studies in fitter patients.

Clinical trial identification

NCT03813836.

Editorial acknowledgement

Legal entity responsible for the study

UCL.

Funding

MSD.

Disclosure

M.D. Forster: Financial Interests, Personal, Advisory Board: Bayer, Merck, MSD, Roche, Takeda, ultrahuman, Transgene, Immunotep, Amgen, BMS, EQRx, GSK, Janssen, Oxford VacMedix, PharmaMar, Regeneron, Syncorp; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, MSD, Merck; Financial Interests, Institutional, Local PI: Roche, Apollomics, Takeda, Ellipsis, Moderna, Exsciencia, ALXOncology, GenMab; Financial Interests, Personal and Institutional, Coordinating PI, Presented data at ESMO-IO 2022: Achilles; Financial Interests, Institutional, Coordinating PI: Oxford VaxMedix, Janssen; Financial Interests, Institutional, Coordinating PI, Presented Data at SITC 2023: Immutep; Non-Financial Interests, Advisory Role, Chair of Scientific Advisory Group: Ruth Strauss Foundation. J.J. Sacco: Financial Interests, Personal, Advisory Board, I have received honoraria for participation on advisory boards, both personal and to institution: Immunocore; Financial Interests, Institutional, Advisory Board: Immunocore, Replimune; Financial Interests, Personal, Advisory Board: Delcath; Financial Interests, Institutional, Local PI: Immunocore, Replimune, Qbiotics, MSD; Financial Interests, Institutional, Research Grant: Immunocore, AstraZeneca, BMS; Other, Travel and conference costs: MSD. A. Ward: Financial Interests, Institutional, Invited Speaker, Invited speaker regarding early adopter experience of Ethos therapy: Varian; Financial Interests, Institutional, Coordinating PI, Acting as lead investigator for commercial trials of Ethos therapy, developing UK ethics approvals: Varian; Non-Financial Interests, Principal Investigator, PI for 2x non commercial head and neck radiotherapy trials: University of Birmingham; Non-Financial Interests, Advisory Role, Member of radiotherapy CRG: NHS England. R. Metcalf: Financial Interests, Personal, Advisory Board: Ayala, Bayer, Aptus Clinical, PCI Biotech, Oxsonics, Roche, Achilles Therapeutics; Financial Interests, Personal, Other, Honoraria: BMS, MSD, Sanofi. R. Begum: Financial Interests, Institutional, Full or part-time Employment: University College London; Financial Interests, Institutional, Funding, Funding for coordination of academically sponsored study: AstraZeneca, Shionogi & Co. Ltd. All other authors have declared no conflicts of interest.