Abstract 1362TiP
Background
In previously treated patients (1 or 2 lines) with MET exon 14 skipping mutated (METex14) advanced non-small cell lung cancer (NSCLC), the evidence of the efficacy of standard therapies (chemotherapy or immunotherapy) is limited. Capmatinib, a MET inhibitor, is approved in the USA, Japan, Hong Kong, and Switzerland for the treatment of adult patients with metastatic METex14 NSCLC, based on the results from the phase II GEOMETRY mono-1 study. Results of this trial demonstrated an overall response rate (ORR) and median overall survival (OS) of 67.9% and 20.8 months in treatment-naive (N=28) and 40.6% and 13.6 months in pretreated (N=69) patients with METex14 NSCLC treated with capmatinib. GeoMETry-III (NCT04427072) is a multicenter, open-label, randomized, global, phase III trial evaluating the efficacy and safety of capmatinib versus docetaxel as second- or third-line therapy in patients with METex14 NSCLC.
Trial design
This study began enrollment in September 2020 and is recruiting adult patients with EGFR wild-type, ALK-rearrangement negative, stage IIIB/IIIC or IV METex14 NSCLC, who have progressed on 1 or 2 prior lines of systemic therapy and are candidates for single-agent docetaxel. Patients with neurologically unstable, symptomatic central nervous system (CNS) metastases or those requiring increasing doses of steroids ≤2 weeks prior to study entry to manage CNS symptoms are excluded. The study aims to enroll around 90 patients, in 2:1 randomization, stratified by number of prior lines (1 or 2) of systemic therapy, to receive oral capmatinib 400 mg twice daily or intravenous docetaxel 75 mg/m2 every 21 days. Patients meeting protocol-specified eligibility criteria can cross over from the docetaxel to the capmatinib arm after blinded independent review committee (BIRC)-confirmed progressive disease as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Study endpoints: Table: 1362TiP
| Category | Endpoint |
| Primary | Progression-free survival (PFS) by BIRC per RECIST 1.1 |
| Key secondary | ORR by BIRC per RECIST 1.1 |
| Secondary | PFS, ORR by investigator Duration of response, time to response, disease control rate by BIRC and investigator OS Safety Pharmacokinetics Patient-reported outcomes Intracranial antitumor activity by BIRC per the Response Assessment in Neuro-Oncology Brain Metastases criteria in patients with baseline CNS lesions |
Clinical trial identification
NCT04427072.
Editorial acknowledgement
Medical editorial assistance was provided by Gowri Natarajan (Novartis Healthcare Pvt. Ltd.).
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
P-J. Souquet: Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Novartis; Financial Interests, Personal, Funding, Research Funding: Novartis. B. Solomon: Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role, Consulting or Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Roche/Genentech; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Amgen; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Lilly; Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: Royalties from Veristrat (Biodesix); Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: UpToDate; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme; Financial Interests, Personal, Other, Honoraria: Roche/Genentech; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Institutional, Funding, Research Funding: Pfizer. J.F. Vansteenkiste: Financial Interests, Institutional, Advisory Role, Consulting or Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role, Consulting or Advisory Role: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role, Consulting or Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role, Consulting or Advisory Role: MSD Oncology; Financial Interests, Institutional, Advisory Role, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role, Consulting or Advisory Role: Roche; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: MSD Oncology; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Institutional, Funding, Research Funding: MSD. M. Carbini: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. A. Jary: Financial Interests, Personal, Full or part-time Employment: Novartis. S. Glaser: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis; Financial Interests, Personal, Stocks/Shares: Alcon. A. Chassot Agostinho: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. J. Wolf: Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Amgen; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Bayer; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Blueprint; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Chugai; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Ignyta; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Janssen; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Loxo; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Novartis; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Roche; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Takeda; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Amgen; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Bayer; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Blueprint; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Boehringer Ingelheim; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Chugai; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Daiichi Sankyo; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Ignyta; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Janssen; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Eli Lilly; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Loxo; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Novartis; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Seattle Genetics; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Takeda; Financial Interests, Institutional, Funding, Research Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Research Funding: Janssen Pharmaceuticals; Financial Interests, Institutional, Funding, Research Funding: Novartis; Financial Interests, Institutional, Funding, Research Funding: Pfizer. All other authors have declared no conflicts of interest.