1391P - Capmatinib vs docetaxel as second- or third-line (2/3L) therapy in patients (pts) with METex14-mutated advanced NSCLC (aNSCLC): The GeoMETry-III trial

Background

Capmatinib (cap), a selective MET inhibitor, is approved by multiple health authorities worldwide, including US, Japan, and EU, in METex14-mutated aNSCLC population, based on the phase 2 GeoMETry mono-1 study (NCT02414139). Here, we report the available efficacy and safety of cap vs docetaxel (doc) from GeoMETry-III trial.

Methods

GeoMETry-III is a multicenter, open-label, randomized, phase 3 trial (NCT04427072). Eligible pts included EGFR wild type, ALK rearrangement−negative, stage IIIB/IIIC or IV METex14–mutated NSCLC who have progressed on 1/2L of systemic therapy. Primary and key secondary endpoints were progression-free survival (PFS) and overall response rate (ORR) by blinded independent review committee (BIRC) assessment per RECIST v1.1, respectively. Although 90 pts were planned to be included in this study, due to slow enrollment, the study was terminated early with 22 patients enrolled.

Results

As of Feb 15, 2023, data cutoff, 22 pts were randomized 2:1 to cap (n = 15) or doc (n = 7) arms. Baseline characteristics were generally comparable between arms. The observed benefit with cap vs doc in median PFS was not statistically significant: 6.1 months vs 4.1 months; HR, 0.46; 95% CI 0.16-1.3; P = 0.066. Of 15 pts in cap arm, 8 had partial response (53.3%, 95% CI 26.6-78.7) vs none in doc arm (95% CI 0-41.0). Disease control rate was 73.3%; 95% CI 44.9-92.2 vs 57.1%; 95% CI 18.4-90.1, respectively. Median duration of response in cap was 9.9 months; 95% CI 2.9-NE. Five of 6 doc-treated pts crossed over to cap (at 1.4, 1.9, 6.0, 6.3, and 13.7 months from doc start due to progression), which confounded the overall survival results. No new safety signals were observed for cap. Most frequent treatment-related AEs (≥25%, any grade) in cap were peripheral edema (46.7%) and nausea (33.3%); and in doc were, alopecia (66.7%), anemia (50.0%), asthenia, conjunctivitis, lacrimation increased, onycholysis (33.3% each).

Conclusions

Overall, the numerical differences in PFS and ORR showed trends favoring cap, and together with safety, are consistent with previous results of the pivotal GeoMETry mono-1 study. The GeoMETry-III trial was terminated early due to enrollment constraints.

Clinical trial identification

NCT04427072.

Editorial acknowledgement

Medical writing support for this abstract was provided by Apra Manral, Novartis Healthcare Pvt. Ltd.

Legal entity responsible for the study

Novartis.

Funding

Novartis.

Disclosure

O.J. Juan Vidal: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck Sharp & Dohme, Lilly, Takeda, AstraZeneca, Janssen; Financial Interests, Personal, Invited Speaker: Roche/Genentech; Financial Interests, Institutional, Funding: AstraZeneca. M.K. Singhal: Financial Interests, Personal, Research Grant, Investigator grant: Novartis, Roche, Pfizer; Financial Interests, Personal, Other, Honorarium: Novartis, Roche, Pfizer, Emcure, MSD, AstraZeneca, Dr Reddys, Intas; Financial Interests, Personal, Other, Travel grant: Dr Reddys Lab, Pfizer, Merck; Financial Interests, Personal, Speaker, Consultant, Advisor: Zydus, Axiom, Lupin. R.M. Alvarez: Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Advisory Board: Boehringer, Novartis, Roche; Financial Interests, Personal, Other, conference registration: MSD Oncology; Financial Interests, Institutional, Coordinating PI: Roche; Financial Interests, Personal and Institutional, Coordinating PI: Janssen Oncology, Rain Therapeutics, Boehringer, Cebiotex, Novartis. P. Souquet: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Research Funding: Novartis; Financial Interests, Personal, Other, Honoraria: Novartis. S. Kim: Financial Interests, Personal, Advisory Role: AstraZeneca, Novartis, Amgen, Eli Lilly, Boehringer Ingelheim; Financial Interests, Personal and Institutional, Research Funding: AstraZeneca, Novartis; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim. A. Robeva, A. Jary, M. Miskic: 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, Alcon.. J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Chugai; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer. All other authors have declared no conflicts of interest.