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E-Poster Display

1284P - MET inhibitor capmatinib plus EGFR tyrosine kinase inhibitor nazartinib for EGFR-mutant non-small cell lung cancer

Date

17 Sep 2020

Session

E-Poster Display

Topics

Tumour Site

Non-Small Cell Lung Cancer

Presenters

Enriqueta Felip

Citation

Annals of Oncology (2020) 31 (suppl_4): S754-S840. 10.1016/annonc/annonc283

Authors

E. Felip1, V. Minotti2, R. Soo3, J. Wolf4, B. Solomon5, D.S.W. Tan6, A. Ardizzoni7, D.H. Lee8, L.V. Sequist9, F. Barlesi10, L. Paz-Ares11, D. Rodriguez-Abreu12, M.R. Garcia Campelo13, M. Sprauten14, L. O’Sullivan Djentuh15, R. Belli16, S. Glaser17, M. Zou18, M. Giovannini19, J.C. Yang20

Author affiliations

  • 1 Department Of Medical Oncology, Vall d’Hebron University Hospital, 8035 - Barcelona/ES
  • 2 Medical Oncology, A O Perugia Osp S Maria Misericordia Loc S Andrea d Fratte, 06132 - Perugia/IT
  • 3 Department Of Haematology-oncology, National University Cancer Institute, 119074 - Singapore/SG
  • 4 Department Of Oncology, Universitaetsklinikum Koeln, 50937 - Cologne/DE
  • 5 Department Of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne/AU
  • 6 Department Of Medical Oncology, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 7 Medical Oncology, A.O.di Bologna Policl.Sant'Orsola-Malpighi-Università Studi, 40138 - Bologna/IT
  • 8 Department Of Oncology, Asan Medical Center, 138-931 - Seoul/KR
  • 9 Cancer Center, Massachusetts General Hospital, 02114 - Boston/US
  • 10 Cnrs, Inserm, Crcm, Aphm, Aix-Marseille University, Marseille/FR
  • 11 Medical Oncology, Hospital Universitario 12 de Octubre, 28041 - Madrid/ES
  • 12 Medical Oncology, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria/ES
  • 13 Deparment Of Medical Oncology, Complejo Uni Hosp A Coruna antes Hospital Juan Canalejo, 15006 - A Coruña/ES
  • 14 Oncology Department, Oslo Universitetssykehus Radiumhospitalet, 0424 - Oslo/NO
  • 15 Gdo Tm Onco, Novartis Pharma AG, Basel/CH
  • 16 Oncology Du Gdd, Novartis Pharma AG, Basel/CH
  • 17 Onco Biostats, Novartis Pharma AG, Basel/CH
  • 18 Opm Translational Precision Oncology, Novartis Pharmaceuticals Corporation, East Hannover/US
  • 19 Oncology Global Development, Novartis Pharmaceuticals Corporation, 07936 - East Hanover/US
  • 20 Department Of Oncology, National Taiwan University Hospital, 100 - Taipei/TW

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Abstract 1284P

Background

In patients (pts) with EGFR-mutant non-small cell lung cancer (NSCLC) progressing on EGFR tyrosine kinase inhibitors (TKIs), the most common (∼60%) resistance mechanism is EGFR T790M mutation followed by MET dysregulation. This multicenter, phase (Ph) 1b/2 study evaluated capmatinib plus nazartinib in pts with EGFR-mutant NSCLC (NCT02335944).

Methods

In Ph 2, stage IIIB/IV NSCLC pts (≥ 18 years; ECOG PS ≤ 1; activating EGFR mut [exon19del and/or L858R]) were treated at the recommended ph 2 dose (RP2D: capmatinib 400 mg twice daily + nazartinib 100 mg once daily). Efficacy and safety are reported for pretreated pts with EGFR TKI resistance, with any T790M/MET (Group 1) and treatment (tx)-naive pts with T790M-, any MET (Group 3). Efficacy was also evaluated as per MET status (MET+: IHC 3+ and/or gene copy number ≥ 4) for a pooled group of pretreated pts from Group 1 and those Ph 1 pts treated at RP2D (Group 1 + Ph 1b RP2D group).

Results

As of Feb 5, 2019, 52 and 47 pts were enrolled in groups 1 and 3, respectively. Group 1 + Ph 1b RP2D group enrolled 68 pts (66 had known MET status: 23 MET+, 43 MET-). Key baseline characteristics are shown in the table. The ORR (primary endpoint) was 28.8% in the pretreated Group 1, 61.7% in the tx-naïve Group 3, and 43.5% and 27.9% in the MET+ and MET- pts in the pretreated combined group, respectively (Table). Key secondary efficacy endpoints are shown in the table. Most frequent (≥30%) any-grade tx-related adverse events (Group 1, 3) were peripheral edema (50%, 57.4%), nausea (42.3%, 48.9%) and diarrhea (23.1%, 46.8%). Table: 1284P

Post-EGFR TKI Tx-naive
Group 1 N = 52 Group 1 + Ph 1b RP2D N = 68 N = 47
MET+ N = 23 MET- N = 43
Baseline characteristics
Caucasian, % 55.8 56.5 46.5 66
Never smokers, % 69.2 69.6 62.8 55.3
≥ 2 prior tx,% 32.7 43.5 30.2 --
Baseline central nervous system metastasis, % 36.5 26.1 37.2 27.7
Primary Efficacy Endpoint
ORR [95% CI], % 28.8 [17.1, 43.1] 43.5 [23.2, 65.5] 27.9 [15.3, 43.7] 61.7 [46.4, 75.5]
Secondary Efficacy Endpoints
Median DOR [95% CI], months 6.3 [3.7, 10.8] 6.3 [3.6, 10.8] 9.3 [3.7, 40.4] 11.6 [6.6, 14.3]
Median PFS [95% CI], months 5.6 [3.7, 7.4] 7.7 [5.4, 12.2] 5.4 [3.5, 6.4] 11.0 [7.6, 13.8]
Median OS [95% CI], months 18.8 [14.9, 21.7] 18.8 [14.0, 21.3] 17.2 [12.5, NE] NE [15.9, NE]

Conclusions

Efficacy observed in tx-naive pts (Group 3) does not seem to support addition of a MET inhibitor to EGFR TKI in MET unselected pts vs EGFR TKI alone. In MET+ pretreated pts, capmatinib plus nazartinib demonstrated clinically relevant efficacy and confirms the role of selective MET inhibition in this subset of post-EGFR TKI pts. Capmatinib plus nazartinib was well tolerated, with similar safety profile across the groups.

Clinical trial identification

NCT02335944.

Editorial acknowledgement

Editorial assistance was provided by Aarti Kamaraj (Novartis Healthcare Pvt. Ltd.).

Legal entity responsible for the study

Novartis Pharmaceuticals.

Funding

Novartis Pharmaceuticals.

Disclosure

E. Felip: Advisory/Consultancy: Pfizer, Roche, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb, Guardant Health, Novartis, Takeda, AbbVie, Blueprint Medicines, Lilly, Merck Kgaa, Merck Sharp & Dohme, Janssen, Samsung ; Speaker Bureau/Expert testimony: Pfizer, Roche, AstraZeneca, Bristol-Myers Squibb, Novartis, Takeda, Lilly, Merck Sharp & Dohme, Medscape, Prime Oncology, Touchtime ; Research grant/Funding (self): Fundación Merck Salud, Grant for Oncology Innovation (GOI) ; Officer/Board of Directors, Independent member: Grífols . R. Soo: Honoraria (self): AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Ignyta, Lilly, Merck, Novartis, Pfizer, Roche, Taiho, Takeda, Yuhan), Honararia (Institution) (AbbVie, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Ignyta, Merck, Merck Serono, Novartis, Pfizer, Roche, Ta; Research grant/Funding (self): AstraZeneca, Boehringer Ingelheim ; Research grant/Funding (institution): AbbVie, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Ignyta, Merck, Merck Serono, Novartis, Pfizer, Roche, Takeda, Yuhan. J. Wolf: Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AbbVie, Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Chugai, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Takeda; Research grant/Funding (institution): BMS, Janssen, Novartis, Pfizer, Roche . B. Solomon: Honoraria (self): Novartis, AstraZeneca, Roche-Genentech, Bristol-MyersSquibb, Merck, Loxo Oncology, Gritstone Oncology ; Honoraria (institution): Pfizer, Bristol-Myers Squibb; Advisory/Consultancy: Novartis, AstraZeneca, Roche-Genentech, Bristol-Myers Squibb, Merck, Loxo Oncology, Gritstone Oncology, Pfizer. D.S.W. Tan: Honoraria (self): Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda; Advisory/Consultancy: Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli-lily, Loxo; Research grant/Funding (self): Novartis, AstraZeneca, GlaxoSmithKline, Bayer, Pfizer; Travel/Accommodation/Expenses: Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche,Takeda. A. Ardizzoni: Honoraria (self): BMS, MSD, Roche, AstraZeneca, Eli Lilly; Research grant/Funding (institution): Celgene, BMS, Ipsen, Roche. D.H. Lee: Non-remunerated activity/ies: Blueprint Medicine, Takeda; Advisory/Consultancy, Personal fees: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, CJ Healthcare, Eli Lilly, ChongKeunDang, Janssen, Merck, MSD, Mundipharma, Novartis, Ono, Pfizer, Roche, Samyang Biopharm, ST Cube, AbbVie, Takeda, Genexine, Menarini, BC Pharma. L.V. Sequist: Research grant/Funding (self): AZ, Merrimack Pharmaceuticals, Genentech, BI, Loxo, Blueprint medicines, Novartis; Advisory/Consultancy: Janssen, AZ, Merrimack Pharmaceuticals, Genentech. F. Barlesi: Honoraria (self): AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda; Honoraria (institution): AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, MedImmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis. L. Paz-Ares: Advisory/Consultancy, Speaker Bureau/Expert testimony, Personal fees (Scientific advice/Speaker): Lilly, MSD, Roche, PharmaMar, Merck, AstraZeneca, Novartis, Boehringer Ingelheim, Celgene, Servier, Sysmex, Amgen, Incyte, Pfizer, Ipsen, Adacap, Sanofi, Bayer, Blueprint, Bristol-Myers Squibb; Research grant/Funding (self): MSD, AstraZeneca, Pfizer, Bristol-Myers Squibb; Advisory/Consultancy, Advisory board: Genomica; Officer/Board of Directors, Co-founder and Board member: Altum Sequencing. D. Rodriguez-Abreu: Honoraria (self), Advisory/Consultancy: Roche, AstraZeneca, Bristol-Myers Squibb, MSD, Eli Lilly, Pfizer, and Novartis; Travel/Accommodation/Expenses: Roche, Bristol-Myers Squibb, MSD and Novartis; Research grant/Funding (self): BMS. M.R. Garcia Campelo: Honoraria (self): MSD, Bristol-Myers, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda; Advisory/Consultancy: MSD, Bristol-Myers, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda; Speaker Bureau/Expert testimony: MSD, Bristol-Myers, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda. M. Sprauten: Honoraria (self): AstraZeneca, Pierre Fabre, Pfizer; Honoraria (institution): Roche, Astra, Pierre Fabre, Pfizer; Advisory/Consultancy: AstraZeneca.L. O’Sullivan Djentuh: Full/Part-time employment: Novartis Pharma AG. R. Belli: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. S. Glaser: Full/Part-time employment: Novartis; Shareholder/Stockholder/Stock options: Novartis, Alcon. M. Zou: Full/Part-time employment: Novartis. M. Giovannini: Full/Part-time employment: Novartis. J.C-H. Yang: Honoraria (self): Boehringer Ingelheim, Eli Lilly, Roche/Genentech/Chugai, MSD, Novartis, BMS, Ono pharmaceutical, AstraZeneca, Takeda Oncology; Advisory/Consultancy: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, MSD, Merck Serono, Pfizer, Novartis, Celgene, Yuhan Pharmaceuticals, BMS, Ono Pharmaceutical, Daiichi Sankyo, AstraZeneca, Takeda Oncology, Blueprint Medicines, Hansoh Pharmaceutical, G1 The. All other authors have declared no conflicts of interest.

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