RETIFANLIMAB for Metastatic upper gastrointestinal cancer | Esophageal cancer | Gastric cancer

Inclusion criteria

• {"criterion_text":"- Patients must provide written informed consent according to ICH/GCP, and national/local regulations prior to any screening procedures."}
• {"criterion_text":"- dMMR identified by IHC of mismatch repair proteins MLH1, PMS2, MSH2 en MSH6"}
• {"criterion_text":"- Primary tumor or metastasis accessible for repeat fresh histological biopsies"}
• {"criterion_text":"- Male or female adult patients (> 18 years)."}
• {"criterion_text":"- Patients with histologically confirmed diagnosis of metastatic or irresectable HER2 negative adenocarcinoma of the stomach or oesophagus, patients with HER2 positive disease are eligible when treatment with trastuzumab is contraindicated."}
• {"criterion_text":"- Patients with metastatic or irresectable adenocarcinoma of the stomach or oesophageal junction (Siewert II or III) not pre-treated with chemotherapy or radiotherapy for irresectable or metastatic disease. Palliative radiotherapy on the primary tumor or a metastatic lesion is allowed if other untreated lesions for RECIST evaluation are present. Chemoradiation with carboplatin area under the curve (AUC) 2 and paclitaxel 50 mg/m2 for irresectable disease is allowed if subsequent disease progression is proven on radiological imaging."}
• {"criterion_text":"- Measurable/evaluable disease as assessed by RECIST 1.1"}
• {"criterion_text":"- ECOG (WHO) performance status 0-2"}
• {"criterion_text":"- Adequate hepatic, renal and hematological function"}

Exclusion criteria

• {"criterion_text":"- Severe renal impairment (CLcr ≤ 30 ml/min)"}
• {"criterion_text":"- Any clinically significant disorder impacting the risk-benefit balance negatively per physician’s judgment."}
• {"criterion_text":"- Presence of additional malignancy that is progressing or has required active treatment in the last 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded."}
• {"criterion_text":"- Active autoimmune disease that has required systemic treatment in past 2 years, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment."}
• {"criterion_text":"- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention."}
• {"criterion_text":"- Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 2."}
• {"criterion_text":"- Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months."}
• {"criterion_text":"- NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings."}
• {"criterion_text":"- Active infection or an unexplained fever >38.5°C (excluding tumor fever), which in the physician’s opinion might compromise the patient’s health."}
• {"criterion_text":"- Current use or any use in last two weeks of strong CYP3A-enzyme, CYP2C8, and/or strong UGT1A inhibitors/inducers."}
• {"criterion_text":"- Known hypersensitivity or contraindications to any of the components of capecitabine or oxaliplatin."}
• {"criterion_text":"- History of severe and unexpected reactions to fluoropyrimidine therapy."}
• {"criterion_text":"- Known complete dihydropyrimidine dehydrogenase (DPD) deficiency."}
• {"criterion_text":"- Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to use a reliable method of birth control, during therapy and for 3 months following the last dose of cytotoxic agents."}
• {"criterion_text":"- Treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine."}
• {"criterion_text":"- Pre-existing motor or sensory neurotoxicity greater than WHO grade 1."}
• {"criterion_text":"- History of organ transplant, including allogeneic stem cell transplantation."}
• {"criterion_text":"- Receiving probiotics as of the first dose of study treatment."}

Primary endpoints

• {"endpoint_text":"- Interferon gamma (IFN-ϒ) expression and number of infiltrating cytotoxic T-cells","definition_or_measurement_approach":"Assessment of IFN-ϒ expression signature and infiltration of cytotoxic T cells in the tumor immune microenvironment at baseline, after two courses of CapOx and after 8 weeks of PD-1 inhibition maintenance using retifanlimab; measured on repeat fresh histological biopsies (per main objective and inclusion requirement for repeat biopsies)."}

Secondary endpoints

• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Progression-free survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Response rate according to RECIST 1.1 or iRECIST","definition_or_measurement_approach":"Response assessed according to RECIST 1.1 or iRECIST."}
• {"endpoint_text":"- Adverse events according to NCI CTCAE version 5.0.","definition_or_measurement_approach":"Adverse events graded/recorded using NCI CTCAE v5.0."}
• {"endpoint_text":"- Quality of life","definition_or_measurement_approach":""}
• {"endpoint_text":"- Percentage of patients proceeding to subsequent lines of treatment after progression and describe the types of subsequent treatments","definition_or_measurement_approach":"Proportion of patients proceeding to subsequent lines and description of subsequent treatment types (as reported)."}
• {"endpoint_text":"- Reasons for forgoing subsequent treatment after progression","definition_or_measurement_approach":""}

Netherlands

Earliest CTIS Part Ii Submission Date

02-04-2024

Latest Decision Or Authorization Date

03-04-2024

Processing Time Days

1

Number Of Sites

6

Number Of Participants

25

Primary sponsor

Full Name

Amsterdam UMC

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands