Phase II single arm study with CABozantinib in Non-Small Cell Lung Cancer patients with MET deregulation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Ricerca Traslazionale

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-02-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518386-95-02

EudraCT number

2017-004157-16

ClinicalTrials.gov

NCT03911193

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy in term of response rate (RR) of Cabozantinib in NSCLC patients with MET amplification or MET exon 14 Skippin mutation pretreated or not with MET inhibitors

Secondary objectives 1

1. Not applicable

Conditions and MedDRA coding

Non small-cell lung cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Citological or histological diagnosis of non-small-cell-lung cancer (NSCLC) stage III B (not suitable for local treatments with curative intent) or stage IV. 2. Tissue samples available for MET analysis (archivial tissue or tissue collected at study entry); patients without archival tumor tissue or refusing new biopsy at study entry, are eligible if MET mutation is detected in cf-DNA 3. Presence of MET mutations (exon 14 skipping mutation ONLY) detected in tissue or in cf-DNA detected at the local lab or MET amplification (MET/CEP7 ratio > 2.2) detected in the central lab ONLY. 4. Measurable disease according to RECIST criteria version 1.1 5. At least 1 prior line of standard therapy (chemotherapy and/ or immunotherapy) 6. Performance status 0-1 (ECOG) 7. Age ≥18 years 8. Patients potentially fertile using adequate methods of contraception in order to avoid childbearing. Contraceptive methods must be respected by male and female patients and their partners during study treatment period and at least 4 months after completing therapy 9. Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to enrollment: a. ANC ≥ 1500 cells/μL without granulocyte colony-stimulating factor support b. Platelet count ≥ 100,000/μL without transfusion c. Hemoglobin ≥ 9.0 g/dL Patients may be transfused to meet this criterion d. AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN, with the following exceptions: - Patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN - Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 × ULN. e. Serum bilirubin ≤ 1.25 × ULN f. Patients with known Gilbert disease who have serum bilirubin level ≤ 3 mg/dL may be enrolled g. Calculated creatinine clearance (CRCL) ≥ 45 mL/min or calculated CRCL must be ≥ 60 mL/min 10. Patient compliance to the study procedure 11. Written informed consent

Exclusion criteria 1

1. 1. Tissue sample not available for the central assessing of MET amplification 2. No possibility to assess MET status 3. Absence of any measurable disease according to RECIST criteria 4. Co-existence of driver events, including EGFR mutations, KRAS mutations, ALK rearrangements or ROS-1 rearrangements 5. No prior therapy 6. Concomitant chemotherapy or immunotherapy or radiotherapy 7. Symptomatic brain metastasis 8. Uncontrolled significant inter-current or recent illness, including cardiovascular disorders and gastro-intestinal disorders 9. Major surgery within 2 months before first dose of study treatment 10. Concomitant anti-coagulation with oral anti-coagulants or plated inhibitors 11. History of significant bleeding, trachea-bronchial tree/major blood vessels invading tumors, cavity pulmonary lesions and GI disorders associated with a risk of perforation or fistula formation 12. Diagnosis of another cancer in the last 3 years, except for in situ carcinoma of cervix, breast and bladder or skin carcinoma (squamous or basalioid) 13. Pregnancy or breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Response Rate (RR) (complete + partial responses) of Cabozantinib in NSCLC patients with MET amplification or MET exon 14 skipping mutation pre-treated or not with MET inhibitors.

Secondary endpoints 1

1. - Progression free survival (PFS) - Overall survival (OS) - Disease Control Rate (DCR: stable disease + partial response + complete response) - Exploratory biomarkers on blood and tissue samples (for each patient enrolled in the study optionally a tissue sample could be provided at disease progression)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Ricerca Traslazionale

Sponsor organisation

Fondazione Ricerca Traslazionale

Address

Via Dei Santi Quattro 61

City

Rome

Postcode

00184

Country

Italy

Scientific contact point

Organisation

Fondazione Ricerca Traslazionale

Contact name

Federico Cappuzzo

Public contact point

Organisation

Fondazione Ricerca Traslazionale

Contact name

Federico Cappuzzo

Locations

1 EU/EEA country · 19 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications