Watch-and-wait strategy to initiate Dostarlimab-based Immunotherapy in localized deficient mismatch repair (dMMR) and/or microsatellite instability high (MSI-H) oEso-gastric junction and gastric adenocarcinoma: An open-label GERCOR phase II study

Phase 1

Recruiting

• Conditions: metastatic gastric cancer; MedDRA version: 21.1Level: PTClassification code: 10063916Term: Metastatic gastric cancer Class: 100000004864; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: CTIS2023-506102-39-00
• Lead Sponsor: Gercor

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-07-14
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 59

Inclusion Criteria

Is capable of giving signed and dated informed consent,, Has adequate liver function: =1.5 x upper limit of normal (ULN) of direct bilirubin = ULN for participants with total bilirubin levels >1.5 x ULN (inclusion possible if known Gilbert syndrome), alkaline phosphatase <5 x ULN, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =2.5 x ULN,, Has international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) =1.5 x ULN, except for the patient on anticoagulant therapy who must have PT-INR-aPTT within therapeutic range is deemed appropriate by the Investigator,, Has radiological tumor assessment at screening performed within 28 days before inclusion according to RECIST version 1.1 by chest, abdomen, and pelvis CT, showing the absence of metastatic or non-surgical disease,, A female participant is eligible to participate if she is not pregnant or breastfeeding,, Male participants are eligible to participate if they agree to the following during the study treatment and for 4 months after the last dose of dostarlimab:, Provides primary tumor tissue samples (processed as formalin-fixed, paraffin-embedded [FFPE] blocks or freshly frozen) acquired during UGI endoscopy together with images (mandatory),, Is willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study,, s registered in a National Health Care System (PUMa - Protection Universelle Maladie included)., Has an ECOG PS of 0-1,, Is between =18 and =75 years old,The patient over 75 years of age is eligible only if all the following conditions are met: The patient’s G8 questionnaire score is above 14 AND The patient is eligible for surgery and has no contraindications to repeated UGI endoscopy with biopsies,, Has histologically proven non-metastatic gastric or OGJ adenocarcinoma cT2 to T4, Nx, M0 after computed tomography thorax-abdomen-pelvis (TAP-CT) and echo-endoscopy (EUS) according to the 7th Edition of the International Union Against Cancer;, Has no peritoneal carcinomatosis (optional coelioscopy; recommended in case of doubt/ suspicious on CT/ imaging),, Has not received prior therapy (chemotherapy, radiotherapy, or immunotherapy) for localized gastric or OGJ adenocarcinoma,, Tumor status confirmed to be dMMR/MSI-H, Has hematological status: absolute neutrophil count (ANC) =1.5 x 109/L; platelets =100 x 109/L; hemoglobin =9 g/dL,, Has adequate renal function: serum creatinine level =150 µM and clearance =50 ml/min (Modification of the Diet in Renal Disease [MDRD] or Cockcroft and Gault),

Exclusion Criteria

Has received prior concomitant unplanned antitumor therapy (e.g., chemotherapy, molecular targeted therapy, immunotherapy),, Has active hepatitis B virus (HBV, defined as having a positive hepatitis B surface antigen [HBsAg] test) or hepatitis C virus (HCV) prior to inclusion,, Patient under a legal protection regime (guardianship, curatorship, judicial safeguard) or administrative decision or incapable of giving his/her consent,, Impossibility of submitting to the medical follow-up of the study for geographical, social, or psychiatric illness., Has pyloric tumor,, Has any history of autoimmune disease including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis,, Has a history of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest imaging,, Has received any live, attenuated vaccine within 14 days prior to the firs dose of study treatment or such administration is anticipated during the study,, Has received prior therapy with any immune-checkpoint inhibitors, including antibodies or drugs targeting CD137, CTLA-4, PD-1, or PD-L1 or other checkpoint pathways,, Has had prior allogeneic bone marrow transplantation or prior solid organ transplantation,, Has received treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to the first dose of adjuvant treatment or is required to receive systemic immunosuppressive medications during the study. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease., Has received treatment with any investigational medicinal product within 28 days prior to study entry,, Has a treatment anticoagulant or hemostasis disorder contraindicating - biopsies during endoscopy,, Has had major surgical procedure within 28 days (4 weeks) prior to the first dose of study treatment,, Has other serious and uncontrolled non-malignant disease (including active infection) or is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active infection requiring systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within 90 days) myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study,, Has other concomitant or previous malignancy other than the disease under study, except as noted below: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer from which the patients was in complete remission for =3 years,, Has metastases (M stage disease) whatever the location,, Is pregnant or bre

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified