Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma

NCT05135845 | Suspended Phase 2 DMC

• 1 other identifier: APHP201152
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Oesophageal Adenocarcinoma; Gastric Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Tumor response

  Overall response rate defined as the proportion of patients with at least one objective tumour response (complete or partial) according to response evaluation criteria in solid tumours (RECIST) v1.1 within 6 months.

  6 months

Secondary Outcomes (7)

• Proportion of unacceptable toxicity of the regimen during the first and second cycles of administration

  Day 42

• Proportion of unacceptable toxicity of the regimen during the whole treatment course

  12 months or treatment discontinuation

• Proportion of patients with adverse events during the whole treatment course

  12 months or treatment discontinuation

• Duration of overall response

  24 months

• Time to response

  24 months

Interventions

Capmatinib DRUG

Capmatinib 400mg BID for a maximum of 12 months or until progression, patient's refusal or unacceptable toxicity

Also known as: INC280

Spartalizumab DRUG

Spartalizumab 300mg Q3W for a maximum of 12 months or until progression, patient's refusal or unacceptable toxicity

Also known as: PDR001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Previous treatment with immunotherapy or MET inhibitor
• Impossibility to take oral medication
• Persistent toxicities related to prior treatment of grade greater than 1
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (7)

Hôpital Jean Minjoz

Besançon, 25030, France

Location

Centre François Leclerc

Dijon, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

AP-HP Hôpital Saint Louis

Paris, 75010, France

Location

Hôpital Haut Lévêque

Pessac, 33604, France

Location

Institut Universitaire du Cancer

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

capmatinib; spartalizumab

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter single-arm adaptive phase II trial with 2 cohorts according to MET amplification level : * Cohort 1: tumor without MET amplification (\< 6 copies); * Cohort 2: tumor with MET amplification (≥6 copies).

Study Record Dates

• First Submitted: October 28, 2021
• First Posted: November 26, 2021
• Study Start: March 22, 2022
• Primary Completion: April 1, 2023
• Study Completion: October 1, 2025
• Last Updated: February 3, 2023

Record last verified: 2023-01

Locations

FR (7)