Temozolomide + Nivolumab in MGMT Methylated Oesophagogastric Cancer

Inclusion Criteria23

• Patients ≥ 18 years of age
• Pathologically confirmed advanced unresectable or metastatic OGA
• MGMT methylation on archival tissue
• Mismatch repair proficient (MSI-normal or MMR intact)
• Previously treated with at least 3 months of platinum and fluoropyrimidine based chemotherapy for advanced disease and without evidence of disease progression.
• Measurable disease per RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Can swallow TMZ capsules
• Adequate organ function assessed within 7 days before randomization:
• White blood cell count (WBC) \> 1.5 x 109/L
• Absolute neutrophil count (ANC) \> 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Haemoglobin ≥ 90 g/L
• Measured/calculated creatinine clearance ≥ 60 mL/min (according to Cockroft-Gault formula).
• Total bilirubin within normal limits (if the patient has documented Gilbert's disease ≤ 1.5 x ULN or direct bilirubin ≤ 1.5 x ULN)
• Aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 1.5 x ULN
• All toxicities (exception alopecia, and grade 2 fatigue, neuropathy and lack of appetite /nausea) attributed to prior anti-cancer therapy must have resolved to grade 1 (NCI CTCAE version 5.0) or baseline before administration of study drug.
• Women of childbearing potential (WOCBP) may be included following a confirmed menstrual period and must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG)). Pregnancy test must be within 24 hours prior to starting treatment. (A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient).
• WOCBP should use one highly effective and one effective method of birth control during the study treatment period and for at least 5 months after the last dose of the study treatment.
• Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 5 months after the last dose of the study treatment.
• Men who are sexually active with a WOCBP must adhere to contraception during and for a period of 7 months after the last dose of the study treatment.
• Absence of any psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Written informed consent