Abstract 1285P
Background
MET exon 14 skipping mutations (METex14) are seen in 3-4% of patients (pts) with non-small cell lung cancer (METex14 NSCLC) and are associated with poor outcomes. In the phase 2 GEOMETRY mono-1 study, capmatinib was efficacious in pts with METex14 NSCLC who were treatment-naive (overall response rate [ORR] 68%) or received one/two lines of therapy (ORR 41%). We present a post-hoc analysis evaluating efficacy and safety of capmatinib in pts with METex14 NSCLC who received immunotherapy (IO) before study entry.
Methods
Cohort 4 (pre-treated METex14 NSCLC) is included in this analysis. Efficacy (ORR and progression-free survival [PFS]) on prior IO, determined by the investigator is reported. Efficacy (ORR, duration of response [DOR] and PFS by blinded independent review committee (BIRC) per RECIST 1.1) of capmatinib 400 mg BID are reported for pts with or without prior IO, as well as safety and biomarker status.
Results
As of 28 October 2019, 69 pts with METex14 NSCLC were enrolled. Of these, 19 had prior IO (median age 71 years; women 63.2%; never smokers 63.2%) and 50 did not (median age 71.5 years; women 56%; never smokers 56%). Of 19 prior IO pts, 9 received IO first-line and 10 second-line, 18/19 received IO monotherapy. 14/19 pts did not respond to IO (8/19 had progressive disease as best overall response). Median PFS on prior IO was 3.29 months (95%CI 2.10-5.16). Efficacy of capmatinib was demonstrated in pts who received and who did not receive prior IO: ORR 57.9% (n=11/19; 95%CI 33.5-79.7) and 34% (n=17/50; 95%CI 21.2-48.8); median DOR 11.20 months (95%CI 3.35-NE) and 7.16 months (95%CI 4.17-11.14), respectively. Durable responses were observed in pts with lack of response/primary resistance to IO. Safety findings with capmatinib for prior IO pts were similar to pts without prior IO. No increased risk of interstitial lung disease/pneumonitis was observed. Average tumor mutation burden was <10 mut/mb in both groups.
Conclusions
Efficacy data of IO in pts with METex14 NSCLC is limited. Capmatinib demonstrated efficacy irrespective of the prior treatment with IO, including in pts with lack of response/primary resistance to IO. Capmatinib was well-tolerated in post IO pts.
Clinical trial identification
NCT02414139.
Editorial acknowledgement
Medical editorial assistance with this abstract was provided by Manojkumar Patel (Novartis Healthcare Pvt. Ltd).
Legal entity responsible for the study
Novartis.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
J.F. Vansteenkiste: Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Novartis; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Roche; Research grant/Funding (institution): MSD. E.F. Smit: Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Takeda; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Regeneron; Advisory/Consultancy: Novartis; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Seattle Genetics. H.J.M. Groen: Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: BMS; Advisory/Consultancy: Merck; Advisory/Consultancy: AbbVie; Research grant/Funding (institution): Boehringer Ingelheim. E.B. Garon: Advisory/Consultancy: Dracen; Advisory/Consultancy: EMD Serono; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Mirati ; Research grant/Funding (institution): Dynavax; Research grant/Funding (institution): Iovance Biotherapeutics; Research grant/Funding (institution): Neon Therapeutics; Research grant/Funding (institution): EMD Serono. R.S. Heist: Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Tarveda ; Research grant/Funding (institution): Apollomics; Honoraria (self): Chugai/Roche; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Mirati Therapeutics; Research grant/Funding (institution): Peregrine Pharmaceuticals; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): Debiopharm Group; Research grant/Funding (institution): Corvus Pharmaceuticals; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Agios; Research grant/Funding (institution): Pfizer. T. Hida: Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): Lilly; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Nippon Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Clovis Oncology; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Kissei Pharmaceutical; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Sumitomo Dainippon Pharma; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Kyowa Hakko Kirin; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Janssen. M. Nishio: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb Japan; Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Takeda; Advisory/Consultancy: Teijin Pharma; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Nippon Kayaku; Research grant/Funding (institution): Merck. K. Kokowski: Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer; Advisory/Consultancy: BMS; Travel/Accommodation/Expenses: Celgene. C. Grohe: Honoraria (self), Advisory/Consultancy: MSD Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self): Lilly; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Takeda. N. Reguart: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche. A.S. Mansfield: Advisory/Consultancy: Trovagene; Advisory/Consultancy: Genentech; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: AbbVie; Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Novartis. A. Robeva: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. S. Ghebremariam: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. M. Waldron-Lynch: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. M. Akimov: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. N. Nwana: Research grant/Funding (self), Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. M. Giovannini: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. J. Wolf: Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Chugai Pharma; Advisory/Consultancy: Ignyta; Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: MSD Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Advisory/Consultancy, Research grant/Funding (self): Janssen; Advisory/Consultancy: Loxo/Lilly; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Amgen; Advisory/Consultancy: Takeda; Advisory/Consultancy: Amgen.