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

• ClinicalTrials.gov Identifier: NCT04926831
• Recruitment Status: Active, not recruiting
• First Posted: June 15, 2021
• Last Update Posted: December 14, 2023
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: capmatinib	Phase 2

Detailed Description:

This trial is a phase II, two cohort study of neoadjuvant capmatinib treatment (pre-surgery) which will be given for 8 weeks prior to a surgical resection and then followed by a three year adjuvant capmatinib treatment (post surgery). Following treatment, there will be a two year survival follow-up. The two molecularly defined cohorts will be enrolled in parallel. Approximately 38 evaluable participants will be enrolled in the study.

During treatment participants will visit their treating physician to assess overall health status which will include lab-work and other safety assessments. Survival follow-up will be every 6 months which can be conducted via a telephone visit for up to approximately 2 years after end of treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: August 10, 2022
• Estimated Primary Completion Date: August 6, 2026
• Estimated Study Completion Date: August 6, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort A; Participants with NSCLC with MET exon 14 skipping mutations, irrespective of MET gene copy number (GCN) will take 400 mg tablet orally twice per day	Drug: capmatinib; 150 mg and 200 mg tablets for oral administration; Other Name: INC280
Experimental: Cohort B; Participants with NSCLC with high level MET amplification will take 400 mg tablet orally twice per day	Drug: capmatinib; 150 mg and 200 mg tablets for oral administration; Other Name: INC280

Outcome Measures

Primary Outcome Measures :

1. Major pathological response (MPR) rate based on local review [ Time Frame: Baseline up to time of surgery (approximately 8 to 10 weeks after first dose) ]
   MPR rate in each cohort defined as the percentage of participants with ≤ 10% residual viable cancer cells

Secondary Outcome Measures :

1. Complete pathologic response (pCR) rate based on central and local review [ Time Frame: Baseline up to time of surgery (approximately. 8- 10 weeks after first dose) ]
   Complete pathologic response (pCR) rate is defined as the percentage of participants with no residual viable cancer cells.
2. Overall response rate (ORR) based on local investigator assessment [ Time Frame: Baseline up to time of surgery (approximately 8 - 10 weeks after first dose) ]
   Overall response rate (ORR) is defined as the percentage participants with best overall response (BOR) of complete response (CR) or partial response ( PR) according to RECIST v1.1
3. Number of adverse events and serious adverse events as assessed by CTCAE criteria [ Time Frame: Baseline up to approximately 40 months ]

   The occurrence of adverse events will be reported from first day of treatment through end of treatment plus 30 days.

   Serious adverse events which are treatment related will be reported through the end of study participation. Adverse events also may be detected or through physical examination findings, laboratory test findings, or other assessments.

4. Disease free survival rate (DFS) from start of adjuvant therapy [ Time Frame: From time of surgery and at 24, 36, and 60 months ]
   Defined as the time from end of surgery (start of adjuvant therapy) until the recurrence of cancer or death due to any cause.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Histologically confirmed NSCLC stage IB-IIIA, N2 and selected IIIB (T3N2 or T4N2)
• Participant must have either MET exon 14 mutations and/or high level MET amplification
• Participants must be eligible for surgery and scheduled for surgical resection within approximately 2 weeks after the last does of neoadjuvant study treatment.

Exclusion Criteria:

• 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
• Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior to starting study treatment, or who have not recovered from side effects of such procedure.
• Prior systemic anti-cancer therapy (chemotherapy, immunotherapy, biologic therapy, vaccine) or investigational agents for NSCLC within the past 3 years.
• History of or current interstitial lung disease or pneumonitis

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

Contacts and Locations

Locations

United States, California

UCLA Oncology Hematology .

La Jolla, California, United States, 92037

University of California Davis Cancer Center .

Sacramento, California, United States, 95817

United States, Virginia

Fairfax-Northern Virginia Hematology-Oncology .

Fairfax, Virginia, United States, 22031

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04926831
• Other Study ID Numbers: CINC280AUS12
• First Posted: June 15, 2021
• Last Update Posted: December 14, 2023
• Last Verified: December 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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/.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

MET exon 14 skipping mutation; High MET amplification; Neoadjuvant; Prior to surgery; Adjuvant; After surgery; INC280; MET inhibition; adult; capmatinib

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases