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P.K. Paik
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MA16 - Novel Strategies in Targeted Therapy (ID 407)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:G. Purkalne, J. Von Pawel
- Coordinates: 12/07/2016, 14:20 - 15:50, Strauss 2
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MA16.09 - Antitumor Activity and Safety of Crizotinib in Patients with MET Exon 14-Altered Advanced Non-Small Cell Lung Cancer (ID 5162)
15:14 - 15:20 | Author(s): P.K. Paik
- Abstract
- Presentation
Background:
MET alterations leading to exon 14 skipping occur in ~4% of non-squamous non‑small cell lung cancer (NSCLCs) and 20–30% of sarcomatoid lung carcinomas, resulting in MET activation and sensitivity to MET inhibitors in vitro.[1–4] Crizotinib, initially developed as a MET inhibitor, is currently approved for the treatment of ALK-rearranged and ROS1-rearranged advanced NSCLC. We present crizotinib antitumor activity and safety data in patients (pts) with MET exon 14-altered advanced NSCLC.
Methods:
Advanced NSCLC pts positive for MET exon 14-alteration status determined locally by molecular profiling were enrolled into an expansion cohort of the ongoing phase I PROFILE 1001 study (NCT00585195) and received crizotinib at a starting dose of 250 mg BID. Objective responses were assessed using RECIST v1.0.
Results:
As of the data cut-off of Feb 01, 2016, 21 pts with MET exon 14-altered NSCLC received crizotinib treatment (18 response-evaluable, 3 not yet evaluable). Median age was 68 y (range: 53−87). Tumor histology was: 76% adenocarcinoma, 14% sarcomatoid adenocarcinoma, 5% adenosquamous carcinoma, and 5% squamous cell carcinoma. Sixty-two percent (62%) of pts were former-smokers, 38% never-smokers, and there were no current smokers. Duration of treatment ranged from 0.2 to 12.2 mo, with 76% of pts (16/21) still ongoing. Five pts discontinued treatment (1 due to AE, 3 due to clinical or disease progression, and 1 preferred alternative treatment formulation). PRs were observed in 8 pts, for an objective response rate of 44% (95% CI: 22–69); 9 pts had stable disease. Median time to response was 7.8 weeks (range: 7.0–16.3), which was the approximate time of the scheduled first on treatment tumor scans for patients. Median progression-free survival could not be calculated. The most common (≥25%) treatment-related AEs (TRAEs) were edema (43%) diarrhea (33%), nausea (33%), vision disorder (33%), and vomiting (29%). Most TRAEs were grade 1/2 in severity and consistent with the known safety profile of crizotinib. Four grade 3 TRAEs (edema, bradycardia, anemia, and weight increased) and no grade 4 or 5 TRAEs were reported. Enrollment of pts with MET exon 14-altered NSCLC continues, and updated data will be available at the time of presentation.
Conclusion:
Crizotinib has clinically meaningful antitumor activity in pts with MET exon 14-altered advanced NSCLC. The drug has a tolerable AE profile, consistent with that previously reported for pts with ALK-rearranged or ROS1-rearranged advanced NSCLC. Further study of crizotinib in this pt population is warranted.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-066 - Phase II Trial of the C-Met Inhibitor Tepotinib in Advanced Lung Adenocarcinoma with MET Exon 14 Skipping Mutations after Failure of Prior Therapy (ID 5626)
14:30 - 14:30 | Author(s): P.K. Paik
- Abstract
Background:
Background: The MET proto-oncogene is activated in 3-4% of lung adenocarcinomas through mutations that lead to aberrant mRNA splicing and skipping of exon 14, which encodes a region of the c-Met protein that regulates its degradation. c-Met lacking exon 14 accumulates as a functional receptor on the cell surface and appears to act as a true oncogenic driver, exclusive of other known oncogenic drivers such as EGFR and ALK. Emerging data suggest that lung adenocarcinomas harboring MET with exon 14-skipping mutations are sensitive to c-Met kinase inhibitors. The highly selective and potent c-Met inhibitor tepotinib has been shown to be well tolerated and active in several phase I/Ib trials, with activity appearing greatest in c-Met-positive tumors. The recommended dose has been established as 500 mg/day. This open-label phase II trial (EudraCT 2015-005696-24) is investigating the efficacy of tepotinib in patients with lung adenocarcinoma harboring MET mutations that cause exon 14 skipping.
Methods:
Trial design: Eligible patients are adults with histologically confirmed stage IIIB/IV lung adenocarcinoma who have failed at least one line of systemic therapy, including a platinum doublet-containing regimen, but have failed no more than two active therapies. Tumors cannot harbor EGFR mutations that confer sensitivity to EGFR TKIs, or ALK rearrangements, but must exhibit MET mutations that are known to lead to exon 14 skipping, confirmed by a central laboratory. The primary objective is to assess the efficacy of tepotinib according to confirmed objective response as per independent review determined by RECIST v1.1. Secondary objectives include further assessment of efficacy, and assessment of safety, pharmacokinetics, and quality of life. Patients receive tepotinib 500 mg/day in 21 day cycles until disease progression, intolerable toxicity, or withdrawal from treatment for other reasons. Recruitment of 60 patients in Europe, USA, and Japan is planned. This trial will establish the activity, safety, and tolerability of tepotinib in patients with lung adenocarcinoma harboring c-Met exon 14 alterations.
Results:
section not applicable
Conclusion:
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