Phase II of Neoadjuvant and Adjuvant Capmatinib in NSCLC (Geometry-N)

Phase II Trial of Neoadjuvant and Adjuvant Capmatinib in Participants With Stages IB-IIIA, N2 and Selected IIIB (T3N2 or T4N2) NSCLC With MET Exon 14 Skipping Mutation or High MET Amplification (Geometry-N)

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.

Study Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: capmatinib

Detailed Description

This was a Phase II, two cohort, two stage study of capmatinib given for 8 weeks (2 cycles) prior to surgical resection, followed by three-year capmatinib treatment in adjuvant setting. Surgery had to be performed up to 2 weeks after the last dose of neoadjuvant study treatment.

There were 2 molecularly defined cohorts enrolled in parallel:

• Cohort A: MET exon 14 skipping mutations, irrespective of MET GCN or
• Cohort B: high level MET amplification (MET: GCN ≥ 10 by FISH or FoundationOne CDx NGS using tumor tissue).

Approximately 42 participants were aimed to be enrolled in the study, with 21 participants per cohort. This was planned to obtain 38 evaluable participants, 19 per each cohort. Participants who had both MET exon 14 skipping mutations and high-level MET amplification were planned to be enrolled into Cohort A. An evaluable subject received the neoadjuvant treatment and subsequently underwent surgery, resulting in a pathological response.

The study recruitment was prematurely discontinued due to significant recruitment challenges leading to termination of the study. The challenges included the rarity of the mutation and site initiation delays caused by staff shortages associated with COVID-19. As a result, only 4 subjects were enrolled and treated in Cohort A.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • UCLA Oncology Hematology
    • La Jolla, California, United States, 92037
      • UCLA Oncology Hematology .
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center .
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Fairfax Northern Virginia Hem Onc .
    • Fairfax, Virginia, United States, 22031
      • Fairfax Northern Virginia Hem Onc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key inclusion criteria:

1. Adult ≥ 18 years of age at the time of informed consent.
2. 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).
3. 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).
4. Participants must be eligible for surgery and scheduled for surgical resection within approximately 2 weeks after the last dose of neoadjuvant study treatment.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.

Key exclusion criteria:

1. 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.
2. Presence or history of a malignant disease that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
3. Prior treatment with any MET inhibitor or HGF-targeting therapy.
4. Participants with other known oncogenic driver alterations.
5. Prior systemic anti-cancer therapy (chemotherapy, immunotherapy, biologic therapy, vaccine) or investigational agents for NSCLC.
6. 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).

Other protocol-defined inclusion/exclusion criteria may apply at the end

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A (MET exon 14 skipping mutations); 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; 150 mg and 200 mg tablets for oral administration; Other Names: INC280
Experimental: Cohort B (high MET amplification); 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; 150 mg and 200 mg tablets for oral administration; Other Names: INC280

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Overall Response Rate (ORR) was defined as the percentage participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response ( PR) according to RECIST v1.1. BOR was the observed response at the assessment performed prior to surgery via local review.	Baseline up to time of surgery (approximately 8 - 10 weeks after first dose)
Complete Pathologic Response (pCR) Rate	Complete pathologic response (pCR) rate ws defined as the percentage of participants with no residual viable cancer cells. pCR rate was assessed via both central and local review.	Baseline up to time of surgery (approximately. 8- 10 weeks after first dose)
Disease Free Survival (DFS)	Disease Free Survival (DFS) was defined as the time from the date of first adjuvant treatment to the date of the first documented disease recurrence as assessed by local investigator radiologically or death due to any cause. In case of non-conclusive radiological evidence, a biopsy was to be performed to confirm recurrence and used as DFS event. DFS events were assessed locally.	From time of surgery to Months 24, 36, and 60
Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. Treatment emergent Adverse Event (TEAEs) in this study were events that started after the first dose of study treatment and until 30 days after the last dose of study treatment, or events present prior to the first dose of treatment which increased in severity based on preferred term within 30 days after the last study treatment.	Baseline up to 30 days after last dose of study medication, assessed up to approximately 20 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2022
• Primary Completion (Actual): March 13, 2024
• Study Completion (Actual): March 13, 2024

Study Registration Dates

• First Submitted: June 14, 2021
• First Submitted That Met QC Criteria: June 14, 2021
• First Posted (Actual): June 15, 2021

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: adult; INC280; Neoadjuvant; Adjuvant; capmatinib; MET exon 14 skipping mutation; High MET amplification; Prior to surgery; After surgery; MET inhibition; Mesenchymal Epithelial Transition (MET)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; capmatinib
• Other Study ID Numbers: CINC280AUS12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No