A Value-Driven Study on Reducing Immune Checkpoint Inhibitor Dosing Frequency in Advanced Cancers

Inclusion Criteria:

1. Provision of informed consent prior to any study-specific procedure
2. Patients with one of the following:

   * 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
3. Measurable disease per RECIST 1.1 criteria
4. ECOG Performance status is 0-2
5. Normal organ and bone marrow function measured within 28 days before the study as defined below:

   * Haemoglobin ≥ 8.0 g/dL and no blood transfusions in the 28 days prior to entry
   * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
   * No features suggestive of MDS/AML on peripheral blood smear
   * White blood cells (WBC) \> 3x10\^9/L
   * Platelet count ≥ 100 x 10\^9/L
   * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
   * AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
   * Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)
6. A life expectancy ≥ 12 weeks in all patients.
7. Females in childbearing age should be using adequate contraceptive measures, should not be breastfeeding and their pregnancy test prior to the start of treatment must be negative. Evidence of non-child-bearing potential is fulfilled by one of the following criteria at screening:
8. The post-menopausal period defined as age ≥50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
9. Women \<50 years old they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range.
10. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not a tubal ligatio
11. Male patients should be willing to use barrier contraception
12. The patient is willing to comply with the protocol during the study including undergoing treatment and scheduled visits and examinations including follow up.
13. At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and is considered suitable for accurate repeated measurements

Exclusion Criteria:

1. Patients who have previously received immune checkpoint inhibitors or investigational monoclonal antibody therapy.
2. 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
3. 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.
4. 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.
5. Severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which based on investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or having active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
6. Autoimmune disorders
7. Males and females of reproductive potential who are not using an effective method of contraception and females who are pregnant or breastfeeding or have a positive serum pregnancy test prior to study entry
8. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
9. Previous allogeneic bone marrow transplant.