Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma (METIMGAST)

Assistance Publique - Hôpitaux de Paris

Status and phase

Suspended

Phase 2

Conditions

Oesophageal Adenocarcinoma

Gastric Adenocarcinoma

Treatments

Drug: Capmatinib

Drug: Spartalizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT05135845

APHP201152

Details and patient eligibility

About

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.

Enrollment

90 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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