Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma

• Status: Not yet recruiting
• Trial end date: 2025-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Spartalizumab

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