593P - MET TKIs in Asian patients (pts) with MET exon 14 skipping NSCLC: A matching-adjusted indirect comparison (MAIC)

Background

Multiple MET TKIs are approved or under regulatory review in Asia for treatment of advanced METex14 NSCLC. However, head-to-head studies are lacking. We conducted MAICs of tepotinib vs savolitinib, gumarontinib, or capmatinib in pts in Asia.

Methods

Pt-level data for pts enrolled in Asia in VISION (tepotinib, global trial; data cut-off: Nov 20, 2022) were reweighted to match the baseline characteristics of the overall populations of NCT02897479 (savolitinib, Asian trial) and GLORY (gumarontinib, Asian trial), and pts enrolled in Asia in GEOMETRY mono-1 Cohorts 4/5b (capmatinib, global trial). Pts were stratified by first-/second- or later-line (1L/2L+). Subgroup analyses evaluated VISION pts with METex14 in tissue biopsies (T+). ORR and PFS by IRC, and OS were compared.

Results

Compared with VISION pts overall (n=313), outcomes were similar in pts enrolled in Asia (n=107), or T+ pts in Asia (n=87). Before reweighting, T+ pts enrolled in Asia had an ORR of 67% (95% CI: 53, 80), median (m) PFS of 16.5 months (11.0, ne [not evaluable]), and mOS of 32.7 months (19.1, ne) in 1L (n=46), and ORR of 49% (34, 64), mPFS of 13.8 months (6.9, ne), and mOS of 23.9 months (19.3, ne) in 2L+ (n=41). After reweighting, PFS and OS appeared longer with tepotinib vs savolitinib and gumarontinib in 1L and 2L+ (Table). PFS also seemed longer with tepotinib vs capmatinib in 1L (tepotinib effective sample size [ESS]=5.6; capmatinib, n=3; mPFS: 49.7 [15.9, ne] vs 5.5 months [4.5, ne]) and 2L+ (tepotinib ESS=29.6; capmatinib, n=17; mPFS: 11.1 [5.6, ne] vs 5.0 months [4.1, ne]). Corresponding capmatinib OS data were not available. Improvements with tepotinib vs comparators were also seen in VISION pts overall and pts in Asia, regardless of T+ status. Table: 593P

nr, not reached.*T+ subgroup of pts enrolled in Asia. ^†Overall population of an Asian trial in T+ pts.

Conclusions

Based on available evidence (with limited capmatinib subgroup size), the MAICs show no clinically relevant differences in ORR and trends for longer PFS and/or OS with tepotinib vs savolitinib, gumarontinib, or capmatinib in pts in Asia in 1L and 2L+.

Clinical trial identification

CrossRef funder ID: 10.13039/100009945.

Editorial acknowledgement

Medical writing assistance was provided by Bhartendu K Srivastava, PhD, of Syneos Health, London, UK.

Legal entity responsible for the study

Merck Healthcare KGaA, Darmstadt, Germany Merck Healthcare KGaA.

Funding

Merck (CrossRef Funder ID: 10.13039/100009945).

Disclosure

Y. Wu: Financial Interests, Personal, Other, Institute grants and personal fees: AstraZeneca, Roche, Boehringer Ingelheim; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, MSD, Eili Lilly, Pfizer. T. Douglas, A. Hatswell: Financial Interests, Personal, Full or part-time Employment: Delta Hat Ltd. Y.A. Yao: Financial Interests, Personal, Full or part-time Employment: Merck Serono Co., Ltd., Beijing, China, an affiliate of Merck KGaA. H. Vioix: Financial Interests, Personal, Full or part-time Employment: Merck. All other authors have declared no conflicts of interest.