Abstract 593P
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
1L | 2L+ | |||
Tepotinib weighted* | Savolitinib † | Tepotinib weighted* | Savolitinib † | |
n/ESS | 22.0 | 28 | 11.4 | 42 |
ORR, % (95% CI) | 67 (54, 81) | 54 (35, 73) | 39 (24, 54) | 53 (37, 68) |
mPFS, mo (95% CI) | 12.6 (10.8, ne) | 6.9 (5.5, 8.4) | 13.8 (11.0, ne) | 7.0 (4.3, 13.8) |
mOS, mo (95% CI) | 28.5 (22.7, ne) | 10.9 (8.2, 22.5) | 20.8 (17.7, ne) | 17.5 (10.9, 31.5) |
1L | 2L+ | |||
Tepotinib weighted* | Gumarontinib † | Tepotinib weighted* | Gumarontinib † | |
n/ESS | 29.3 | 46 | 14.1 | 38 |
ORR, % (95% CI) | 69 (56, 83) | 71 (56, 83) | 52 (37, 68) | 60 (44, 75) |
mPFS, mo (95% CI) | 22 (8.3, ne) | 11.8 (8.6, ne) | 11.1 (5.5, ne) | 7.6 (4.1, 9.7) |
mOS, mo (95% CI) | nr (13.8, ne) | nr (16.9, ne) | 36.4 (12.3, ne) | 16.2 (11.7, ne) |
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.
Resources from the same session
101P - The coexistence of TP53 gain-of-function mutation and hypermethylation as a poor prognostic factor in BRAF wild-type metastatic colorectal cancer
Presenter: Kota Ouchi
Session: Poster Display
Resources:
Abstract
102P - Enhancing colorectal cancer prevention in high-risk populations through faecal immunochemical test surveillance
Presenter: Li Xie
Session: Poster Display
Resources:
Abstract
103P - Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort A
Presenter: Junwei Wu
Session: Poster Display
Resources:
Abstract
104P - The value of functional MR-imaging signature model for early prediction of chemotherapy response and its guidance for regimen adjustment to improve efficacy
Presenter: Wenhua Li
Session: Poster Display
Resources:
Abstract
105P - A single-arm, phase II, multicenter study of iparomlimab (QL1604) in patients (pts) with unresectable/metastatic deficient mismatch repair (dMMR)/microsatellite instability high (MSI-H) solid tumors
Presenter: Weijian Guo
Session: Poster Display
Resources:
Abstract
106P - Efficacy and safety of IBI351 (GFH925) monotherapy in metastatic colorectal cancer harboring KRASG12C mutation: Updated results from a pooled analysis of two phase I studies
Presenter: Ying Yuan
Session: Poster Display
Resources:
Abstract
107P - Tumor-stromal ratio in a new age fibroblast activated protein PET imaging as a biomarker for prediction of response to neoadjuvant chemoradiotherapy in carcinoma rectum
Presenter: swetha Suresh
Session: Poster Display
Resources:
Abstract
108P - Detection of HER2 overexpression in colorectal cancer: Comparison of a HANDLE classic NGS panel with standard IHC/FISH
Presenter: Lijuan Luan
Session: Poster Display
Resources:
Abstract
109P - Early onset metastatic colorectal cancer: Clinical-prognostic characteristics and correlation to molecular status
Presenter: Andrea Pretta
Session: Poster Display
Resources:
Abstract
110P - The correlation between multi-dimensional characteristics of circulating tumor cells (CTC) and treatment response in patients with initially unresectable metastatic colorectal cancer
Presenter: Yu Liu
Session: Poster Display
Resources:
Abstract