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.
Provision of informed consent prior to any study-specific procedure
Cohort A: Previously untreated locally advanced/metastatic HER2 -ve gastric/gastroesophageal junction/esophageal (PDL1 CPS ≥5% adenocarcinomas not amenable to curative surgery or radiotherapy who are above to begin platinum double and nivolumab.
Cohort B: Previously untreated locally advanced/metastatic Child's A hepatocellular carcinoma not amenable to curative surgery or radiotherapy who are above to begin atezolizumab and bevacizumab.
Cohort C: Previously untreated locally advanced/metastatic lung adenocarcinoma (PDL1 TPS≥50%, EGFR/ALK wildtype) not amenable to curative surgery or radiotherapy who are above to begin pembrolizumab monotherapy
Patients who have previously received immune checkpoint inhibitors or investigational monoclonal antibody therapy.
Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years
Unstable spinal cord compression/brain metastases unless asymptomatic and not requiring steroids for at least 2 weeks prior to the start of study treatment. For patients with brain metastases, gamma knife or stereotactic brain surgery is allowed prior to study treatment.
Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. Minor surgery is allowed.
Parallel
Extended Dosing Interval - A
DrugNivolumab 360mg 6 weekly (up to 2 years) + XELOX Nivolumab 240mg 4 weekly (up to 2 years) + FOLFOX
Extended Dosing Interval - B
DrugBevacizumab + Atezolizumab 1200mg 6 weekly (up to 2 years)
Extended Dosing Interval - C
DrugPembrolizumab 200mg 6 weekly (up to 2 years)
Standard of Care - A
DrugNivolumab 360mg 3 weekly (up to 2 years) + XELOX Nivolumab 240mg 2 weekly (up to 2 years) + FOLFOX
Standard of Care - B
DrugBevacizumab + Atezolizumab 1200mg 3 weekly (up to 2 years)
Standard of Care - C
DrugPembrolizumab 200mg 3 weekly (up to 2 years)
6
Treatment groupsSee each treatment group below.
Progression-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).
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
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
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.
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)
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