Geometry-N: Phase II of Neoadjuvant and Adjuvant Capmatinib in NSCLC
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|
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.
Arms and Interventions
|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
150 mg and 200 mg tablets for oral administration
|Experimental: Cohort B
Participants with NSCLC with high level MET amplification will take 400 mg tablet orally twice per day
150 mg and 200 mg tablets for oral administration
Primary Outcome Measures
- Major pathological response (MPR) rate based on local review [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
- Complete pathologic response (pCR) rate based on central and local review [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 [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 [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 [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.
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.
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
|1||UCLA Oncology Hematology||La Jolla||California||United States||92037|
|2||University of California Davis Cancer Center||Sacramento||California||United States||95817|
|3||Dana Farber Cancer Center||Boston||Massachusetts||United States||02215|
|4||University of Michigan Health System||Ann Arbor||Michigan||United States||48109-0391|
|5||Memorial Sloan Kettering||New York||New York||United States||10017|
|6||Irving Pavilion; Diabetes Research Unit||New York||New York||United States||10032-3784|
|7||University of Texas MD Anderson Cancer Center||Houston||Texas||United States||77030|
|8||Fairfax-Northern Virginia Hematology-Oncology||Fairfax||Virginia||United States||22031|
Sponsors and Collaborators
- Novartis Pharmaceuticals
Study Documents (Full-Text)None provided.