388P - Capmatinib in Chinese adults with EGFR wt, ALK rearrangement negative (ALK-R−), MET exon 14 skipping mutation (METex14), advanced NSCLC: Results from the phase II GEOMETRY-C study

Background

To date, there is no approved targeted therapy for treatment-naive patients (pts) with METex14 NSCLC in China. Capmatinib, a selective MET inhibitor (METi), is approved for use in this population in >40 countries worldwide, including the US and EU. We report the efficacy and safety of capmatinib as monotherapy in treatment-naive Chinese pts with MET-mutated, advanced NSCLC.

Methods

In this ongoing, multicenter, 2-cohort study (treatment-naive [cohort 1] or pretreated [cohort 2]), Chinese pts aged ≥18 years with EGFR wt, ALK-R−, stage IIIB/IIIC/IV, METex14 NSCLC received capmatinib 400 mg twice daily. Pts pretreated with any METi were excluded. The primary endpoint was overall response rate (ORR) by blinded independent review committee (BIRC) assessment per RECIST 1.1. Secondary endpoints, among others, included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Here, we describe the results of the primary analysis from cohort 1.

Results

As of data cutoff (DCO), April 18, 2022, 15 pts (median [min-max] age: 66 [61-74] years; female: 53.3%; never smokers: 66.7%; brain metastasis: 33.3% at baseline) were enrolled between Jun-Nov 2021. Primary objective was met: ORR by BIRC was 53.3% (8/15; 95% CI: 26.6, 78.7). As of DCO, medians were not reached for DOR, PFS, and OS, with median follow-up time of 4.0, 4.1, and 5.0 months, respectively. Investigator-assessed ORR was 60% (9/15; 95% CI: 32.3, 83.7); disease control rate, by BIRC and investigator assessment, was 86.7% (13/15; 95% CI: 59.5, 98.3). The median (min-max) duration of exposure to study treatment was 21 (1-42) weeks. The incidence of treatment-related adverse events (TRAEs) was 73.3% (11/15); grade 3/4 TRAEs: 20% (3/15); no fatal TRAEs. The most common TRAEs (≥20%; any grade) were peripheral edema (26.7%), increased alanine aminotransferase, and hypoalbuminemia (20% each). No AEs led to study drug discontinuation.

Conclusions

This primary analysis based on ORR shows that capmatinib delivers a high response rate and manageable safety profile in Chinese pts. The short follow-up does not allow for conclusions on durability of response or other time-related parameters.

Clinical trial identification

NCT04677595.

Editorial acknowledgement

The authors received medical writing and editorial support for this abstract from Indumathy Pinnamaneni (CONEXTS, Medical and Knowledge Solutions, Novartis Healthcare Pvt. Ltd., Hyderabad, India).

Legal entity responsible for the study

Novartis.

Funding

Novartis.

Disclosure

Y. Wu: Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Pfizer; Financial Interests, Personal, Principal Investigator: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Hengrui, MSD, Pfizer, Sanofi, Roche; Financial Interests, Personal, Other, Honoraria for lecture and presentations.: AstraZeneca, Boehringer Ingelheim, BMS; Financial Interests, Personal, Other, Honoraria for lecture and presentations: Eli Lilly, Hengrui, MSD, Pfizer, Sanofi, Roche. J. Zhao, J. Hu, J. Wu, Y. Xu, Z. Yang, Z. Liu, L. Jiang, J. Chen, Y. Yu, M. Huang, X. Dong, L. Liu, W. Feng, L. Wu, S. Cang, H. Chen: Financial Interests, Personal, Principal Investigator: Novartis. J. Sun, Q. Xie: Financial Interests, Personal, Full or part-time Employment: Novartis.