METIMGAST: Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma

Sponsor
Assistance Publique - Hôpitaux de Paris (Other)
Overall Status
Recruiting
CT.gov ID
NCT05135845
Collaborator
(none)
90
7
42.3
12.9
0.3

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
90 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Intervention Model Description:
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).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).
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Trial to Evaluate the Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma
Actual Study Start Date :
Mar 22, 2022
Anticipated Primary Completion Date :
Apr 1, 2023
Anticipated Study Completion Date :
Oct 1, 2025

Outcome Measures

Primary Outcome Measures

  1. Tumor response [6 months]

    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.

Secondary Outcome Measures

  1. Proportion of unacceptable toxicity of the regimen during the first and second cycles of administration [Day 42]

    Presence of at least one of (composite endpoint): Adverse event (AE) grade >3 (NCI-CTCAE v5), at least possibly related to the treatment or unrelated to disease, progression, intercurrent illness, concomitant medications Non-hematological AE grade ≥3 Recurring grade 2 pneumonitis, Myocarditis grade ≥2 Autoimmune hemolytic anemia, hemolytic uremic syndrome, acquired hemophilia grade ≥3 Guillain-Barre, severe peripheral or autonomic neuropathy, transverse myelitis, encephalitis, aseptic meningitis Laboratory abnormality grade ≥3 for >7days (except nephritis grade 3-4, combined elevations of aspartate or alanine transaminase and total bilirubin, hyperglycemia, serum electrolytes/enzymes changes without clinical impact) Febrile neutropenia, documented infection with absolute neutrophil count<10^9/L, grade 3 neutropenia >7days, grade 4 neutropenia or thrombocytopenia, or bleeding with platelet transfusion AE with discontinuation >21days Significant drug-related AE

  2. Proportion of unacceptable toxicity of the regimen during the whole treatment course [12 months or treatment discontinuation]

    Presence of at least one of (composite endpoint): Adverse event (AE) grade >3 (NCI-CTCAE v5), at least possibly related to the treatment or unrelated to disease, progression, intercurrent illness, concomitant medications Non-hematological AE grade ≥3 Recurring grade 2 pneumonitis, Myocarditis grade ≥2 Autoimmune hemolytic anemia, hemolytic uremic syndrome, acquired hemophilia grade ≥3 Guillain-Barre, severe peripheral or autonomic neuropathy, transverse myelitis, encephalitis, aseptic meningitis Laboratory abnormality grade ≥3 for >7days (except nephritis grade 3-4, combined elevations of aspartate or alanine transaminase and total bilirubin, hyperglycemia, serum electrolytes/enzymes changes without clinical impact) Febrile neutropenia, documented infection with absolute neutrophil count<10^9/L, grade 3 neutropenia >7days, grade 4 neutropenia or thrombocytopenia, or bleeding with platelet transfusion AE with discontinuation >21days Significant drug-related AE

  3. Proportion of patients with adverse events during the whole treatment course [12 months or treatment discontinuation]

    All adverse events during the whole treatment course

  4. Duration of overall response [24 months]

    Time between the first occurrence of tumor objective response, partial or complete (RECIST 1.1) and the first radiological progression, with response assessment every 9 weeks, up to 24 months

  5. Time to response [24 months]

    Time between inclusion and the first occurrence of tumor objective response (complete or partial, according to RECIST 1.1) or the end of the study, with response assessment every 9 weeks, up to 24 months

  6. Progression-free survival [24 months]

    Time between inclusion and the date of the first radiological progression (according to RECIST 1.1), death (any cause), or last follow-up (maximum=24 months), whichever occurs first.

  7. Overall survival [24 months]

    Time between inclusion and death (any cause) or last follow-up (maximum=24 months), whichever occurs first

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Hôpital Jean Minjoz Besançon France 25030
2 Centre François Leclerc Dijon France
3 Centre Léon Bérard Lyon France 69008
4 AP-HP Hôpital Saint Louis Paris France 75010
5 Hôpital Haut Lévêque Pessac France 33604
6 Institut Universitaire du Cancer Toulouse France 31059
7 Institut Gustave Roussy Villejuif France 94805

Sponsors and Collaborators

  • Assistance Publique - Hôpitaux de Paris

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT05135845
Other Study ID Numbers:
  • APHP201152
First Posted:
Nov 26, 2021
Last Update Posted:
May 17, 2022
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of May 17, 2022