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DOI: 10.1055/s-0039-3403367
Capmatinib (INC280) in patients (pts) with METex14-mutated advances NSCLC: an update from phase 2 GEOMETRY mono-1 study
Publication History
Publication Date:
28 February 2020 (online)
Background: Capmatinib is a highly potent and selective MET inhibitor. Previous analysis of GEOMETRY mono-1 study demonstrated a clinically meaningful response rate and manageable toxicity profile in pts with METΔex14-mutated NSCLC who received either 1 – 2 prior lines of treatment (tx) (Cohort 4) or were tx-naïve (Cohort 5b). Here we report the updated results in METΔex14-mutated NSCLC including preliminary data on DOR and PFS.
Methods: GEOMETRY mono-1 is a phase 2, multi-cohort, multicenter study evaluating capmatinib in pts with METΔex14-mutated or MET-amplified advanced NSCLC across 7 cohorts. Pts (≥ 18 years) with ECOG PS 0 – 1, ALK and EGFR wt, and stage IIIB/IV NSCLC were eligible. Pts with METΔex14 mutation (centrally confirmed) were assigned (regardless of MET amplification status/gene copy number) to Cohorts 4 and 5b and received capmatinib tablets 400 mg BID. Primary endpoint was overall response rate (ORR) by BIRC per RECIST v1.1. Key secondary endpoint was DOR by BIRC.
Results: As of Apr 15, 2019, 97 pts with METΔex14-mutated NSCLC (Cohort 4: 69 pts; Cohort 5b: 28 pts) were evaluable for efficacy. ORR by BIRC was 40.6% in Cohort 4 and 67.9% in Cohort 5b. While still immature at the time of this analysis, data on durability are very promising: median DOR by BIRC was 9.72 and 11.14 mo for Cohorts 4 and 5b, respectively; median PFS by BIRC was 5.42 and 9.69 mo for Cohorts 4 and 5b, respectively. High concordance with investigator assessment was observed ([Table 1]). Safety profile remains favourable and unchanged. Most common AEs (≥ 25% all grades) across all cohorts (n = 334), were peripheral edema (41.6%) and nausea (33.2%); majority of the AEs were grade 1/2.
Cohort 4 (2/3 L) (n = 69) |
Cohort 5b (1 L) (n = 28) |
|||
---|---|---|---|---|
BIRC |
Investigator |
BIRC |
Investigator |
|
ORR, % (95% CI) |
40.6 (28.9 – 53.1) |
42 (30.2 – 54.5) |
67.9 (47.6 – 84.1) |
60.7 (40.6 – 78.5) |
Median DOR (95% CI), mo |
9.72 (4.27 – 11.14) |
8.31 (4.34 – 12.06) |
11.14 (5.55-NE) |
13.96 (4.27-NE) |
Median PFS (95% CI), mo |
5.42 (4.17 – 6.97) |
4.80 (4.11 – 7.75) |
9.69 (5.52 – 13.86) |
11.14 (5.52 – 15.24) |
Conclusion: With this update capmatinib continues to demonstrate clinically meaningful efficacy in pts with METΔex14-mutated NSCLC with a manageable toxicity profile.