combination of capmatinib + spartalizumab in advanced oesogastric adenocarcinoma

Conditions: Oesophageal Adenocarcinoma; Gastric Adenocarcinoma

Summary: immunotherapy with anti-pd1 antibodies provides encouraging results on a subset of patients. capmatinib, a met inhibitor, has shown an imunomodulatory effect and a synergy with spartalizumab a pd-1 inhibitor. the purpose of this phase ii trial is to evaluate the efficacy and safety of the combination of capmatinib + spartalizumab in adult patients with advanced oesogastric adenocarcinoma.


Eligibility criteria:
inclusion criteria: * histologically or cytologically documented locally advanced or metastatic oesogastric adenocarcinoma. * unresectable tumor. * patients must have received at least one prior systemic chemotherapy based on platinium salt and fluoropyrimidine with documented progression during chemotherapy. * patients must have received trastuzumab in case of her2 positive tumor (her2 +++ or her2++ and fish or sish+) * determination of tumor met amplification by fish available * ecog performance status ≤ 1. * measurable tumoral disease according to recist 1.1 criteria. * patients must be willing and able to swallow and retain oral medication. * age ≥18 years. * women of childbearing potential and males who are sexually active must agree to follow instructions for method(s) of contraception for the duration of study treatments with capmatinib and spartalizumab until 7 days after the last dose of capmatinib and 150 days after the last dose of spartalizumab * consent to participate in the trial after information * affiliated to a social security system exclusion criteria: * previous treatment with immunotherapy or met inhibitor * impossibility to take oral medication * persistent toxicities related to prior treatment of grade greater than 1 * presence or history of another malignant disease that has been diagnosed and/or required therapy within the past 3 years. exceptions to this exclusion include: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type. * use of any live vaccines within 4 weeks of initiation of study treatment. * history of severe hypersensitivity reactions to other monoclonal antibodies (mabs). * history or current interstitial lung disease or non-infectious pneumonitis * active autoimmune disease or a documented history of autoimmune disease (patients with vitiligo, controlled type i diabetes mellitus on stable insulin dose, residual autoimmune-related hypothyroidism only requiring hormone replacement or psoriasis not requiring systemic treatment are permitted). * allogenic bone marrow or solid organ transplant * uncontrolled active infection * human immunodeficiency virus (hiv) infection * untreated active hepatitis b infection (hbsag positive) (patients with active hepatitis b (hbsag positive) may be enrolled provided viral load (hbv dna) at screening is \<100 ui/ml. patients may receive antiviral treatment with lamivudine, tenofovir, entecavir, or other antiviral agents before the initiation of study treatment to suppress viral replication). * untreated active hepatitis c (hcv rna positive) (patients that achieved a sustained virological response after antiviral treatment and show absence of detectable hcv rna ≥6 months after cessation of antiviral treatment are eligible) * untreated or symptomatic central nervous system (cns) lesion. however, patients are eligible if: a) all known cns lesions have been treated with radiotherapy or surgery and b) patient remained without evidence of cns disease progression ≥4 weeks after treatment and c) patients must be off corticosteroid therapy for ≥2 weeks * clinically significant, uncontrolled heart diseases * recent acute coronary syndrome or unstable ischemic heart disease * congestive heart failure ≥ class iii or iv as defined by new york heart association * long qt syndrome (\> 480 ms in women and 470 ms in men), family history of idiopathic sudden death or congenital long qt syndrome. * uncontrolled hypertension defined by a systolic blood pressure (sbp) ≥150 mm hg and/or diastolic blood pressure (dbp) ≥ 100 mm hg, with or without antihypertensive medication. initiation or adjustment of antihypertensive medication(s) is allowed prior to screening * surgery less than 4 weeks * radiotherapy less than 2 weeks * pregnancy or breastfeeding or women of child-bearing potential, unless they are using highly effective methods of contraception. * sexually active males unless they use a condom during intercourse while taking capmatinib and for 7 days after stopping treatment and should not father a child in this period. * participants receiving treatment with strong inducers of cyp3a and could not be discontinued ≥ 1 week prior to the start of treatment. * systemic chronic steroid therapy (\>10 mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date of first dose of study treatment. * patient having out of range laboratory values defined as: * total bilirubin \>2 mg/dl, except for patients with gilbert's syndrome who are excluded if total bilirubin \>3.0 x uln or direct bilirubin \>1.5 x uln * alanine aminotransferase (alt) \> 3 x uln * aspartate aminotransferase (ast) \> 3 x uln * coagulation: prothrombin time (pt) \>4 seconds more than the uln or international normalized ratio (inr) \>1.7 * absolute neutrophil count (anc) \<1.5 x 109/l * platelet count \<75 x 109/l * hemoglobin \<9 g/dl * creatinine clearance (calculated using cockcroft-gault formula, or measured) \<45 ml/min * serum lipase \>1 uln * cardiac troponin i (ctni) elevation \>2 x uln * potassium, magnesium, phosphorus, total calcium (corrected for serum albumin) outside of normal limits (patients may be enrolled if corrected to within normal limits with supplements during screening) * patients under legal protection * participation to another interventional study with treatment