Pneumologie 2020; 74(S 01): 134
DOI: 10.1055/s-0039-3403367
Posterbegehung (PO25) – Sektion Pneumologische Onkologie
NSCLC: Systemtherapie bei molekularem Treiber
Georg Thieme Verlag KG Stuttgart · New York

Capmatinib (INC280) in patients (pts) with METex14-mutated advances NSCLC: an update from phase 2 GEOMETRY mono-1 study

J Wolf
1   Center for Integrated Oncology, University Hospital Cologne
,
T Seto
2   National Hospital Organization Kyushu Cancer Center
,
JY Han
3   National Cancer Center
,
N Reguart
4   University Hospital Clinic of Barcelona
,
EB Garon
5   University of California
,
HJ Groen
6   University of Groningen and University Medical Center Groningen
,
DSW Tan
7   National Cancer Centre Singapore
,
T Hida
8   Aichi Cancer Center
,
M de Jonge
9   Erasmus MC Cancer Institute
,
SV Orlov
10   St Petersburg Pavlov State Medical University
,
EF Smit
11   Netherlands Cancer Institute
,
P Souquet
12   University Hospital of Lyon-Sud
,
J Vansteenkiste
13   Gasthuisberg University Hospital
,
S Le Mouhaer
14   Novartis Pharma S. A.S,
,
A Robeva
15   Novartis Pharmaceuticals Corporation
,
M Waldron-Lynch
16   Novartis Pharma AG
,
A Balbin
17   Novartis Institutes for Biomedical Research
,
L Fairchild
17   Novartis Institutes for Biomedical Research
,
M Giovannini
15   Novartis Pharmaceuticals Corporation
,
RS Heist
18   Massachusetts General Hospital
› Author Affiliations
Further Information

Publication History

Publication Date:
28 February 2020 (online)

Also available at
 
 

    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.

    Table 1 

    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.


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