Abstract 536TiP
Background
MET amplification (METamp) is a resistance mechanism to EGFR tyrosine kinase inhibitors (TKIs) occurring via over activation of downstream signaling pathways such as PI3K and MAPK. METamp occurs in ≈10% of patients receiving erlotinib, gefitinib, afatinib, or icotinib, and is the most common resistance mechanism to osimertinib in phase III trials, occurring in ≈19% of patients. Tepotinib, an oral once daily potent and selective MET inhibitor, is associated with improved survival in combination with gefitinib in patients with EGFR-mutant MET-amplified NSCLC with EGFR TKI resistance compared with standard chemotherapy in the INSIGHT study (NCT01982955): investigator-reported progression free survival (PFS) was 21.2 vs 4.2 months (HR 0.13; 90% CI 0.04, 0.43) and overall survival, (OS) was 37.3 vs. 13.1 months (HR 0.08; 90% CI 0.01, 0.51).
Trial design
INSIGHT 2 (NCT03940703) is a global single-arm, open-label, phase II trial of tepotinib in patients with advanced (stage IIIB/IV) NSCLC with resistance to 1st–3rd generation EGFR TKIs driven by METamp. Eligibility criteria include patients aged ≥18 years with advanced EGFR-mutant NSCLC and known T790M status, having acquired resistance to EGFR TKIs, and are METamp positive by plasma ‘liquid’ biopsy, with an ECOG PS of 0 or 1 and normal organ function. Prior immunotherapy is permitted but prior MET pathway-targeted therapy is not. Tepotinib (500 mg orally once daily) in combination with osimertinib (80 mg once daily) will be administered until disease progression, unacceptable toxicity, or withdrawal of consent. An initial safety run-in will comprise 6 patients (endpoint; dose-limiting toxicities); anticipated full enrollment is 90 patients. The primary endpoint is objective response rate (ORR) by independent review committee (RECIST v1.1). Secondary objectives include investigator-assessed ORR, duration of response, disease control, PFS, OS, pharmacokinetics, health-related quality of life, tolerability, and safety (NCI-CTCAE v5.0). Recruitment is ongoing and approximately 80 study sites in 17 countries in Europe, Asia, and North America are expected to participate in this study.
Clinical trial identification
NCT03940703.
Legal entity responsible for the study
Merck Healthcare KGaA.
Funding
Merck Healthcare KGaA.
Disclosure
J.C-H. Yang: Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Roche/Genentech/Chugai; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Merrimack; Honoraria (self), Advisory / Consultancy: Yuhan Pharmaceuticals; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo ; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Takeda Oncology; Honoraria (self), Advisory / Consultancy: Blueprint Medicines; Honoraria (self), Advisory / Consultancy: Hansoh Pharmaceuticals. B. Ellers-Lenz: Full / Part-time employment: Merck Healthcare KGaA. J. Straub: Full / Part-time employment: Merck Healthcare KGaA. A. Johne: Full / Part-time employment: Merck Healthcare KGaA. Y-L. Wu: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self): Pierre Fabre; Honoraria (self): Sanofi.
Resources from the same session
74TiP - Phase I study of BI 836880, a VEGF/Ang2-blocking nanobody®, as monotherapy and in combination with BI 754091, an anti-PD-1 antibody, in Japanese patients (pts) with advanced solid tumours
Presenter: Kentaro Yamazaki
Session: Poster display session
Resources:
Abstract
75P - A parallel deep learning network framework for whole-body bone scan image analysis
Presenter: Xiaorong Pu
Session: Poster display session
Resources:
Abstract
76P - Perception and satisfaction of cancer patients in clinical trials
Presenter: Jukyung Jeon
Session: Poster display session
Resources:
Abstract
77P - A prognostic nomogram for the prediction of neuroblastoma
Presenter: Jian-Guo Zhou
Session: Poster display session
Resources:
Abstract
80P - The clinical usefulness of a new fat-dissociation method to detect lymph nodes from surgically resected specimen in colorectal cancer: Prospective randomized study
Presenter: Shiki Fujino
Session: Poster display session
Resources:
Abstract
81P - Concurrent or consolidation chemotherapy during radiation as neoadjuvant treatment for locally advanced rectal cancer: A propensity score analysis from two prospective study
Presenter: JianWei Zhang
Session: Poster display session
Resources:
Abstract
82P - Body mass index, tumour location, and colorectal cancer survival
Presenter: Dake Chu
Session: Poster display session
Resources:
Abstract
83P - Helicobacter bilis may play a role in the carcinogenesis of colitis associated colon cancer correlating to increased number of CD4+CD45RB+ T cells
Presenter: Xiangsheng Fu
Session: Poster display session
Resources:
Abstract
84P - Comprehensive evaluation of relapse risk (CERR) score for colorectal liver metastases development and validation
Presenter: Jianmin Xu
Session: Poster display session
Resources:
Abstract
85P - Which is the best partner for capecitabine-based neoadjuvant chemoradiotherapy in locally advanced rectal cancer? A retrospective analysis of a comprehensive cancer center
Presenter: Jingwen Wang
Session: Poster display session
Resources:
Abstract