Phase II of Neoadjuvant and Adjuvant Capmatinib in NSCLC

NCT04926831 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: CINC280AUS12
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 6

Brief Summary

This study was planned to determine if neoadjuvant capmatinib could improve the major pathological response (MPR) in patients with Stage IB-IIIA, N2 and selected IIIB (T3N2 or T4N2) lung cancers with Mesenchymal Epithelial Transition (MET) exon 14 mutations and/or high MET amplification beyond those achieved with surgery, chemotherapy, and radiation. Treatment was to be continued with capmatinib in the adjuvant setting to evaluate the potential clinical benefit of extended therapy. The purpose of this study is to determine if neoadjuvant capmatinib can improve outcomes in participants with stages I-IIIA non-small cell lung cancer with MET exon 14 mutations and/or high MET amplification beyond those achieved with surgery, chemotherapy, and radiation.

Conditions

Non-small Cell Lung Cancer

Keywords

Mesenchymal Epithelial Transition (MET); MET exon 14 skipping mutation; High MET amplification; Neoadjuvant; Prior to surgery; Adjuvant; After surgery; INC280; MET inhibition; adult; capmatinib

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response (MPR) Rate

  The primary efficacy variable was MPR rate, defined as the proportion of participants with ≤ 10% residual viable cancer cells. MPR rate was to be assessed via local review for primary analysis. MPR assessment in tumor samples was collected at time of resection. Due to low number of participants and limited data, analysis related to the primary endpoint was not performed.

  Baseline up to time of surgery (approximately 8 to 10 weeks after first dose)

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  Baseline up to time of surgery (approximately 8 - 10 weeks after first dose)

• Complete Pathologic Response (pCR) Rate

  Baseline up to time of surgery (approximately. 8- 10 weeks after first dose)

• Disease Free Survival (DFS)

  From time of surgery to Months 24, 36, and 60

• Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria

  Baseline up to 30 days after last dose of study medication, assessed up to approximately 20 months

Study Arms (2)

Cohort A (MET exon 14 skipping mutations)

EXPERIMENTAL

The study treatment started on Cycle 1 Day 1 with the first administration of capmatinib 400 mg twice a day (b.i.d.). The participants were planned to receive study treatment for a maximum of 3 years following surgery or until early discontinuation.

Drug: capmatinib

Cohort B (high MET amplification)

EXPERIMENTAL

The study treatment started on Cycle 1 Day 1 with the first administration of capmatinib 400 mg twice a day (b.i.d.). The participants were planned to receive study treatment for a maximum of 3 years following surgery or until early discontinuation.

Drug: capmatinib

Interventions

capmatinib DRUG

150 mg and 200 mg tablets for oral administration

Also known as: INC280

Cohort A (MET exon 14 skipping mutations); Cohort B (high MET amplification)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult ≥ 18 years of age at the time of informed consent.
• Histologically confirmed NSCLC Stage IB-IIIA, N2 and selected IIIB (T3N2 or T4N2) (per AJCC 8th edition), deemed suitable for primary resection by treating surgeon (T4 tumors with mediastinal organ invasion were not eligible for enrollment).
• Participant must have MET exon 14 mutation and/or high-level MET amplification (MET: GCN ≥ 10) as determined by a CLIA certified laboratory. High level MET amplification must be identified by FISH in a CLIA certified laboratory or FoundationOne CDx NGS (other NGS-based methods without adjusting for tumor content % cannot be accepted).
• Participants must be eligible for surgery and scheduled for surgical resection within approximately 2 weeks after the last dose of neoadjuvant study treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.

You may not qualify if:

• Participants with unresectable or metastatic disease. All participants should have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment to exclude brain metastasis.
• Prior treatment with any MET inhibitor or HGF-targeting therapy.
• Participants with other known oncogenic driver alterations.
• Prior systemic anti-cancer therapy (chemotherapy, immunotherapy, biologic therapy, vaccine) or investigational agents for NSCLC.
• Participants with known hypersensitivity to capmatinib and any of the excipients of capmatinib (crospovidone, mannitol, microcrystalline cellulose, povidone, sodium lauryl sulfate, magnesium stearate, colloidal silicon dioxide, and various coating premixes).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (6)

UCLA Oncology Hematology .

La Jolla, California, 92037, United States

Location

UCLA Oncology Hematology

La Jolla, California, 92037, United States

Location

University of California Davis Cancer Center .

Sacramento, California, 95817, United States

Location

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

Fairfax Northern Virginia Hem Onc .

Fairfax, Virginia, 22031, United States

Location

Fairfax Northern Virginia Hem Onc

Fairfax, Virginia, 22031, United States

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

capmatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 14, 2021
• First Posted: June 15, 2021
• Study Start: August 10, 2022
• Primary Completion: March 13, 2024
• Study Completion: March 13, 2024
• Last Updated: October 16, 2025
• Results First Posted: March 26, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

US (6)