Abstract 26P
Background
Capmatinib is a selective MET inhibitor, approved for patients (pts) with METex14 metastatic NSCLC. Its efficacy and safety have been reported for Tx-naive and pretreated pts from the multicohort phase II GEOMETRY mono-1 study. Here we provide primary efficacy data from Cohort 7, as additional first-line (1L) data, in Tx-naive pts with METex14 aNSCLC.
Methods
GEOMETRY mono-1 enrolled pts into several cohorts. Cohorts 5b (mature data previously presented) and 7 comprised Tx-naive pts with METex14 NSCLC. Evaluated outcomes included: Overall response rate (ORR; primary endpoint), median duration of response (mDOR), and median progression-free survival (mPFS), all by blinded independent central review; median overall survival (mOS); and adverse events (AEs). Data cutoff: Aug 30, 2021.
Results
In Cohort 7, 32 Tx-naive pts received capmatinib 400 mg twice daily. ORR was 68.8% (95% CI, 50.0-83.9), with mDOR of 16.59 months (95% CI, 8.34-not estimable [NE]). mPFS was 12.45 months (95% CI, 6.87-20.50) and mOS was not reached yet. Efficacy results for the 2 Cohorts of Tx-naive pts are shown in the table. In Cohort 7, AEs of any grade, regardless of causality, occurred in 31 pts (96.9%), including 26 pts (81.3%) with grade 3/4 AEs. Tx-related AEs (TRAEs) occurred in 29 pts (90.6%), including 18 (56.3%) with grade 3/4; TRAEs led to dose adjustment/interruption in 23 pts (71.9%) and Tx discontinuation in 6 (18.8%) pts. Common TRAEs (≥20%, all grades) were peripheral edema (59.4%), nausea (37.5%), and increased blood creatinine (28.1%). Peripheral edema led to Tx discontinuation in 2 pts (6.3%). Table: 26P
| Cohort 7 n=32 | Cohort 5b* n=28 | |
| ORR, % (95% CI) | 68.8 (50.0-83.9) | 67.9 (47.6-84.1) |
| mDOR, months (95% CI) | 16.59 (8.34-NE) (not mature) | 12.58 (5.55-NE) |
| mPFS, months (95% CI) | 12.45 (6.87-20.50) | 12.42 (8.21-23.39) |
| mOS, months (95% CI) | NE (12.85-NE) (not mature) | 20.76 (12.42-NE) |
*Mature data previously presented
Conclusions
Primary efficacy analysis for Cohort 7 confirms previous findings from Cohort 5b in Tx-naive pts with METex14, showing an ORR of ∼70% and mPFS of >1 year. Safety data are consistent with previously published data for all pts. These data continue to support the use of capmatinib for 1L Tx of pts with METex14 aNSCLC.
Clinical trial identification
NCT02414139.
Editorial acknowledgement
Azka Ashraf, of Chameleon Communications, London, UK, provided medical writing assistance, which was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceutical Corporation.
Disclosure
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. E.B. Garon: Financial Interests, Personal, Other, Consulting or advisory role: ABL Bio; Financial Interests, Personal, Other, Consulting or advisory role: Boehringer Ingelheim; Financial Interests, Personal, Other, Consulting or advisory role: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting or advisory role: Dracen Pharmaceuticals; Financial Interests, Personal, Other, Consulting or advisory role: Eisai; Financial Interests, Personal, Other, Consulting or advisory role: Eli Lilly; Financial Interests, Personal, Other, Consulting or advisory role: EMD Serono; Financial Interests, Personal, Other, Consulting or advisory role: Gilead; Financial Interests, Personal, Other, Consulting or advisory role: GSK; Financial Interests, Personal, Other, Consulting or advisory role: Merck; Financial Interests, Personal, Other, Consulting or advisory role: Natera; Financial Interests, Personal, Other, Consulting or advisory role: Novartis; Financial Interests, Personal, Other, Consulting or advisory role: Personalis; Financial Interests, Personal, Other, Consulting or advisory role: Regeneron; Financial Interests, Personal, Other, Consulting or advisory role: Sanofi; Financial Interests, Personal, Other, Consulting or advisory role: Shionogi; Financial Interests, Personal, Other, Consulting or advisory role: Xilio Therapeutics; Financial Interests, Institutional, Other, Grant / Research support: ABL Bio; Financial Interests, Institutional, Other, Grant / Research support: AstraZeneca; Financial Interests, Institutional, Other, Grant / Research support: Bristol Myers Squibb; Financial Interests, Institutional, Other, Grant / Research support: Dynavax Technologies; Financial Interests, Institutional, Other, Grant / Research support: EMD Serono; Financial Interests, Institutional, Other, Grant / Research support: Genentech; Financial Interests, Institutional, Other, Grant / Research support: Iovance Biotherapeutics; Financial Interests, Institutional, Other, Grant / Research support: Eli Lilly; Financial Interests, Institutional, Other, Grant / Research support: Merck; Financial Interests, Institutional, Other, Grant / Research support: Mirati Therapeutics; Financial Interests, Institutional, Other, Grant / Research support: Neon Therapeutics; Financial Interests, Institutional, Other, Grant / Research support: Novartis. H.J.M. Groen: Financial Interests, Institutional, Funding, Grants or contracts : Boehringer Ingelheim; Financial Interests, Institutional, Other, Consulting fees: Novartis; Financial Interests, Institutional, Other, Consulting fees: Eli Lilly; Financial Interests, Institutional, Other, Consulting fees: Boehringer Ingelheim; Financial Interests, Institutional, Other, Consulting fees: Merck; Financial Interests, Institutional, Other, Consulting fees: Bristol Myers Squibb. D.S.W. Tan: Financial Interests, Institutional, Funding, Research funding: AstraZeneca; Financial Interests, Institutional, Funding, Research funding: Pfizer; Financial Interests, Institutional, Funding, Research funding: ACM Biolabs; Financial Interests, Institutional, Funding, Research funding: Amgen; Financial Interests, Personal, Other, Consulting / advisory role: Pfizer; Financial Interests, Personal, Other, Consulting / advisory role: Novartis; Financial Interests, Personal, Other, Consulting / advisory role: Takeda; Financial Interests, Personal, Other, Consulting / advisory role: Boehringer Ingelheim; Financial Interests, Personal, Other, Consulting / advisory role: Merck; Financial Interests, Personal, Other, Consulting / advisory role: Amgen; Financial Interests, Personal, Other, Consulting / advisory role: AstraZeneca; Financial Interests, Personal, Other, Consulting / advisory role: DKSH; Financial Interests, Personal, Other, Consulting / advisory role: Roche; Financial Interests, Personal, Other, Consulting / advisory role: C4 Therapeutics; Financial Interests, Personal, Other, Consulting / advisory role: GSK. A. Robeva: Financial Interests, Personal, Full or part-time Employment: Novartis. M. Carbini: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board : Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. A. Yovine: Financial Interests, Personal, Full or part-time Employment: Novartis. R. Heist: Financial Interests, Personal, Other, Consulting: Novartis; Financial Interests, Personal, Other, Consulting: Daichii Sankyo; Financial Interests, Personal, Other, Consulting: EMD Serono; Financial Interests, Personal, Other, Consulting: AbbVie; Financial Interests, Institutional, Funding, Research funding to institution: AbbVie; Financial Interests, Institutional, Funding, Research funding to institution: Agios; Financial Interests, Institutional, Funding, Research funding to institution: Corvus; Financial Interests, Institutional, Funding, Research funding to institution: Incyte; Financial Interests, Institutional, Funding, Research funding to institution: Novartis; Financial Interests, Institutional, Funding, Research funding to institution: Lilly; Financial Interests, Institutional, Funding, Research funding to institution: Mirati; Financial Interests, Institutional, Funding, Research funding to institution: Turning Point; Financial Interests, Institutional, Funding, Research funding to institution: Daichii Sankyo. All other authors have declared no conflicts of interest.