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 )

Tracking Information

• First Submitted Date: June 14, 2021
• First Posted Date: June 15, 2021
• Last Update Posted Date: December 14, 2023
• Actual Study Start Date: August 10, 2022
• Estimated Primary Completion Date: August 6, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 14, 2021)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 14, 2021)

• 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.
• 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
• 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.
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase II of Neoadjuvant and Adjuvant Capmatinib in NSCLC
• 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)
• 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.

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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer

Intervention

Drug: capmatinib

150 mg and 200 mg tablets for oral administration

Other Name: INC280

Study Arms

• 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
  Intervention: Drug: capmatinib
• Experimental: Cohort B
  Participants with NSCLC with high level MET amplification will take 400 mg tablet orally twice per day
  Intervention: Drug: capmatinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 13, 2023): 4
• Original Estimated Enrollment (submitted: June 14, 2021): 38
• Estimated Study Completion Date: August 6, 2026
• Estimated Primary Completion Date: August 6, 2026 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04926831
• Other Study ID Numbers: CINC280AUS12
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

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/.

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: December 2023