This is an open-label, single-arm, Phase 2 study of pembrolizumab plus platinum and gemcitabine (PG) in subjects with recurrent or metastatic head and neck cancer squamous cell carcinoma (R/M HNSCC). Evaluable 63 subjects with R/M HNSCC will be enrolled for examination of the efficacy and safety of the combination of pembrolizumab (200 mg IV on Day 1 of each 3-week cycle, up to 35 cycles) in combination with platinum (either cisplatin at 35 mg/m2 IV using a split-dose regimen on Day 1 and Day 8 or carboplatin at AUC 5 IV on Day 1 of each 3-week cycle, up to 6 cycles) and gemcitabine at 1250 mg/m2 IV on Day 1 and 8 of each 3-week cycle, for up to 6 cycles as first-line treatment. This study will be conducted in conformance with Good Clinical Practices. Specific procedures to be performed during the trial, as well as their prescribed timelines and associated visit windows, are outlined in the protocol.
Subject may not have had prior systemic therapy administered in the recurrent or metastatic setting. Systemic therapy which was completed more than 6 months prior to signing consent if given as part of multimodal treatment for locally advanced disease is allowed.
The eligible primary tumour locations are oropharynx, oral cavity, hypopharynx, and larynx.
Subject may not have a primary tumour location site of nasopharynx (any histology).
A male participant must agree to use a contraception as detailed in Appendix 3: Contraceptive Guidance and Pregnancy Testing of this protocol starting with the first dose of study treatment through the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
Has disease that is suitable for local therapy administered with curative intent.
Has progressive disease within six months of completion of curatively intended treatment for locoregionally advanced HNSCC.
Patient with an expected life expectancy of less than 3 months.
A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment allocation (see Appendix 4). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Single group
Pembrolizumab
DrugPembrolizumab 200mg will be administered on Day 1 every 3 weeks for up to 24months
Cisplatin
DrugCisplatin at 35 mg/m2 IV using a split dose regimen on Day 1 and Day 8 of each 3-week cycle, up to 6 cycles.
Carboplatin
DrugCarboplatin at AUC 5 IV on Day 1 of each 3-week cycle, up to 6 cycles.
Gemcitabine
DrugGemcitabine 1250mg/m2 IV on Day 1 and Day 8 of each 3-week cycle, up to 6 cycles
Objective Response Rate (ORR)
To determine Objective Response Rate (ORR) per RECIST 1.1 to treatment of pembrolizumab plus platinum and gemcitabine in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients.
Overall Survival (OS)
1\) To evaluate the Overall Survival (OS) to combination treatment of pembrolizumab plus platinum and gemcitabine in R/M HNSCC patients
Incidence of Treatment-Related Adverse Events (Safety and tolerability)
To evaluate the number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Progression Free Survival (PFS)
2\) To estimate Progression Free Survival (PFS) per RECIST 1.1 to combination treatment of pembrolizumab plus platinum and gemcitabine in R/M HNSCC patients
Response duration (DOR)
3\) To estimate response duration (DOR) per RECIST 1.1 to combination treatment of pembrolizumab plus platinum and gemcitabine in R/M HNSCC patients
Genetic variation
To explore correlation between genetic variation and clinical response of patients.
Microbiome profiling
To conduct on-treatment microbiome profiling and determine the correlation with clinical response
Circulatory immune cells correlations
To explore the changes in circulatory immune cells throughout the treatment period of patients
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University of Malaya
Lead sponsor
Cancer Research Malaysia
Collaborator
Kuala Lumpur General Hospital
Collaborator
National Cancer Institute, Malaysia
Collaborator
Merck Sharp & Dohme LLC
Collaborator
My Starfish Foundation
Collaborator
Yayasan Sime Darby
Collaborator
Yayasan PETRONAS
Collaborator
