This study is a prospective, open label, multi-centre phase 2 trial which assesses the efficacy and safety of standard dosing compared to extended dosing interval of nivolumab, atezolizumab or pembrolizumab in advanced/unresectable gastric/gastroesophageal junction/oesphageal adenocarcinomas with PDL1 CPS ≥5%, hepatocellular carcinoma andnon-small cell lung cancer with PDL1 TPS≥50% with no prior treatment. The investigators hypothesize that nivolumab, pembrolizumab and atezolizumab can be used efficiently at extended dosing intervals, compared to their approved labels with comparable clinical outcome.
This study aims to assess the noninferiority of progression free survival of standard dosing compared to extended dosing interval of nivolumab, pembrolizumab and atezolizumab in advanced/unresectable gastric/gastroesophageal junction/oesphageal adenocarcinomas with PDL1 CPS ≥5%, hepatocellular carcinoma, and non-small cell lung cancer with PDL1 TPS≥50%. Secondary Objective * To investigate the safety, overall survival (OS) of ICI at extended dosing interval of the standard versus extended dosing interval groups. * To investigate the pharmacokinetics (PK) of nivolumab, atezolizumab or pembrolizumab.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
360
Nivolumab 360mg 6 weekly (up to 2 years) + XELOX Nivolumab 240mg 4 weekly (up to 2 years) + FOLFOX
Bevacizumab + Atezolizumab 1200mg 6 weekly (up to 2 years)
Pembrolizumab 200mg 6 weekly (up to 2 years)
Nivolumab 360mg 3 weekly (up to 2 years) + XELOX Nivolumab 240mg 2 weekly (up to 2 years) + FOLFOX
Bevacizumab + Atezolizumab 1200mg 3 weekly (up to 2 years)
Pembrolizumab 200mg 3 weekly (up to 2 years)
Department of Hematology-Oncology, National University Hospita
Singapore, Singapore
RECRUITINGProgression-free survival (PFS)
PFS is defined as the time from date of first dosing until the date of objective disease progression as defined by Response Evaluation Criteria in Solid Tumor (RECIST 1.1) or death (by any cause in the absence of progression).
Time frame: Up to 2 years
Number of participant with treatment related haematological and non-haematological toxicities
As defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time frame: Up to 2 years
Objective response rate
Percentage of patients who have at least one confirmed response of 'complete response' or 'partial response' as defined by Response Evaluation Criteria in Solid Tumor (RECIST 1.1), that is confirmed at least 4 weeks later
Time frame: Up to 2 years
Duration of Response
Duration of response will be defined as the time from the date of first documented response, that is subsequently confirmed until the date of documented progression or death in the absence of disease progression, the end of response should coincide with the date of progression or death from any cause used for the PFS endpoint.
Time frame: Up to 2 years
Disease control rate
Disease control rate is defined as the proportion of patients with a best overall response of CR = complete response, PR = partial response, or SD = stable disease, as defined by Response Evaluation Criteria in Solid Tumor (RECIST 1.1)
Time frame: Up to 2 years
Overall survival
Overall survival will be assessed based on the date of first dose and survival status at the time of analysis.
Time frame: Up to 2 years
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