Pembrolizumab (MK-3475) plus platinum and gemcitabine as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (PIPER): a phase 2, multicentre, single-arm protocol study in Malaysia

• Published in: BMJ open Vol. 14; no. 12; p. e076898
• Main Authors: Cheong, Sok Ching, Selvam, Bawani, Ho, Gwo Fuang, Muhamad Nor, Ibtisam, Tan, Chih Kiang, Wong, Yoke Fui, Teo, Soo Hwang, Lim, Kue Peng, Chai, Annie Wai Yeeng, Yahya, Abqariyah, Wan Ishak, Wan Zamaniah
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 03.12.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Adult; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asian people; Biomarkers; Biomedical research; Cancer; CHEMOTHERAPY; Cisplatin - administration & dosage; Cisplatin - therapeutic use; Clinical trials; Clinical Trials, Phase II as Topic; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Female; Gemcitabine; Head & neck cancer; Head & neck tumours; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - pathology; Humans; IMMUNOLOGY; Immunotherapy; Informed consent; Malaysia; Male; Metastasis; Middle Aged; Monoclonal antibodies; Multicenter Studies as Topic; Neoplasm Recurrence, Local - drug therapy; Oncology; Patient safety; Pregnancy; Protocol; Response rates; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - drug therapy; Targeted cancer therapy; Throat cancer; Toxicity; Malaysia; CHEMOTHERAPY; Head & neck tumours; IMMUNOLOGY
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2023-076898

IntroductionTreatment combination of pembrolizumab plus platinum and 5-fluorouracil (PF) has increased the survival of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The combination of platinum and gemcitabine (PG) has been shown to be superior to PF in the treatment of R/M nasopharyngeal carcinoma patients. Therefore, we hypothesise that the combination of pembrolizumab with PG would be comparable to pembrolizumab with PF as a first-line treatment in R/M HNSCC.Methods and analysisThis is an open-label, multicentre, single-arm, phase 2 study of pembrolizumab plus PG for first-line treatment in subjects with R/M HNSCC in Malaysia. The study is conducted using the Optional Simon optimal 2-stage design. At the initial stage, 26 subjects will be enrolled and if seven or more patients achieve an objective response rate (ORR), then 63 patients will be enrolled. Subjects will be given pembrolizumab 200 mg3 every 3 weeks up to 35 cycles in combination with chemotherapy for up to six cycles of platinum (either cisplatin at 35 mg/m2 intravenous on day 1 and day 8 or carboplatin at area under the curve 5 intravenous on day 1 of each 3-week cycle) and gemcitabine at 1250 mg/m2 intravenous on days 1 and 8 of a 3-week cycle. The primary end point is the ORR as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary end points include the overall survival, progression free survival, response duration and safety. The exploratory objectives include relationships of microbiome profiles, prognostic and predictive biomarkers with the clinical responses.Ethics and disseminationThe study was approved by the ethics committee of the University Malaya Medical Centre (202213–10884). Findings will be disseminated through conference presentations and peer review publications.Trial registration numberClinicalTrials.gov (www.clinicaltrial.gov); NCT05286619.