Clinical trial NCT04926831: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-06-15
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Major Pathological Response (MPR) Rate
timeFrame: Baseline up to time of surgery (approximately 8 to 10 weeks after first dose)
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Baseline up to time of surgery (approximately 8 - 10 weeks after first dose)
measure: Complete Pathologic Response (pCR) Rate
timeFrame: Baseline up to time of surgery (approximately. 8- 10 weeks after first dose)
measure: Disease Free Survival (DFS)
timeFrame: From time of surgery to Months 24, 36, and 60
measure: Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria
timeFrame: Baseline up to 30 days after last dose of study medication, assessed up to approximately 20 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCLA Oncology Hematology .
state: California
city: La Jolla
country: United States
facility: UCLA Oncology Hematology
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center .
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Fairfax
country: United States
facility: Fairfax Northern Virginia Hem Onc .
state: Virginia
city: Fairfax
country: United States
facility: Fairfax Northern Virginia Hem Onc
state: Virginia
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: