Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma

Gastric Adenocarcinoma Clinical Trial

— METIMGAST  

Official title:

Phase II Trial to Evaluate the Combination of Capmatinib + Spartalizumab in Advanced Oesogastric Adenocarcinoma

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05135845
• Other study ID #: APHP201152
• Status: Suspended
• Phase: Phase 2
• Start date: March 22, 2022
• Est. completion date: October 2025

Study information

• Verified date: January 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 90
• Est. completion date: October 2025
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Adenocarcinoma
• Oesophageal Adenocarcinoma

Intervention

Drug:
• Capmatinib
Capmatinib 400mg BID for a maximum of 12 months or until progression, patient's refusal or unacceptable toxicity
• Spartalizumab
Spartalizumab 300mg Q3W for a maximum of 12 months or until progression, patient's refusal or unacceptable toxicity

Locations

Country	Name	City	State
France	Hôpital Jean Minjoz	Besançon
France	Centre François Leclerc	Dijon
France	Centre Léon Bérard	Lyon
France	AP-HP Hôpital Saint Louis	Paris
France	Hôpital Haut Lévêque	Pessac
France	Institut Universitaire du Cancer	Toulouse
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Proportion of unacceptable toxicity of the regimen during the first and second cycles of administration	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	Day 42
Secondary	Proportion of unacceptable toxicity of the regimen during the whole treatment course	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	12 months or treatment discontinuation
Secondary	Proportion of patients with adverse events during the whole treatment course	All adverse events during the whole treatment course	12 months or treatment discontinuation
Secondary	Duration of overall response	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	24 months
Secondary	Time to response	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	24 months
Secondary	Progression-free survival	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.	24 months
Secondary	Overall survival	Time between inclusion and death (any cause) or last follow-up (maximum=24 months), whichever occurs first	24 months