Abstract 3990
Background
MET is a potential therapeutic target in advanced HCC; tepotinib is a highly selective MET inhibitor. Here we report final analysis results from a single-arm multicenter phase 2 study investigating the efficacy and safety of tepotinib in pts with sorafenib-treated advanced MET+ HCC (NCT02115373).
Methods
Adults with advanced MET+ HCC, Child-Pugh Class A, Eastern Cooperative Oncology Group performance status 0–1, and ≥4 weeks of prior sorafenib therapy were eligible for treatment. MET status was assessed by immunohistochemistry (2+ or 3+) and in-situ hybridization. Pts received tepotinib at the recommended phase 2 dose (RP2D) of 500 mg once-daily. The primary endpoint was progression-free survival status at 12 weeks; secondary endpoints included safety and other efficacy parameters.
Results
49 pts had received treatment; median (range) duration of therapy was 3.02 (0.03–16.49) months. Median (range) age was 66 (19–82) years and most patients were male (83.7%). The null hypothesis that the rate of progression-free subjects at 12 weeks is ≤ 15% has been rejected as 31/49 pts (63.3%; 90% confidence interval [CI]: 50.5, 74.7) were progression-free at 12 weeks; median PFS was 3.4 months (90% CI: 2.8, 4.2). Overall, there were 4/49 responders (8.2%; 90% CI: 2.8, 17.7; 1 complete and 3 partial responses). Median overall survival was 5.6 months (90% CI: 5.1, 8.2 months). The most common treatment-related adverse events (AEs) were peripheral edema (n = 32; 38.8%), fatigue (n = 10; 18.4%) and diarrhea (n = 16; 16.3%). 17 pts (34.7%) discontinued treatment due to AEs and 1 pt (2%) died from a treatment-related AE (hypoglycemic coma).
Conclusions
These data indicate that tepotinib has anti-tumor activity in pretreated MET+ advanced HCC and was well tolerated at the RP2D, with no new safety signals detected.
Clinical trial identification
NCT02115373.
Legal entity responsible for the study
Merck KGaA, Darmstadt, Germany.
Funding
Merck KGaA, Darmstadt, Germany.
Editorial Acknowledgement
Medical writing assistance (funded by Merck KGaA, Darmstadt, Germany) was provided by Martin Quinn, PhD of Bioscript Science (Macclesfield, UK).
Disclosure
C. Barone: Advisory board membership, Fee for presentation: Merck Serono. M. Wermke: Honaries: BMS, Novartis, Roche, Bayer, Glenmark, AstraZeneca; Travel reimbursements: AstraZeneca, BMS, MSD, Novartis, Glenmark; Research funding: Novartis, Pfizer. P. Merle: Advisory board member: Bayer, Ipsen, BMS. J.F. Blanc: Advisory board member: Bayer, Lilly Oncology, BMS, Onxeo, Esai, Ipsen. R. Bruns, J. Straub: Employee: Merck KGaA. C. Zhao: Employee: EMD Serono Inc. S. Faivre: Consultant, Clinical trials grants: Blueprint, BMS, Bayer Pharma, Eli Lilly, Ipsen, Merck Serono, MSD, Novartis. All other authors have declared no conflicts of interest.
Resources from the same session
4784 - Tranilast inhibits TGF-beta-induced EMT and invasion/metastasis via the suppression of Smad4 in lung cancer cell lines.
Presenter: Koji Takahashi
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
767 - Integrin beta-like 1 overexpression stimulates invasiveness of ovarian cancer cells in vitro
Presenter: Alexander Cortez
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
938 - MiR-449a suppresses endometrial cancer invasion and metastasis by targeting NDRG1
Presenter: Lihua Qiu
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4866 - Cancer-associated fibroblasts-derived VEGFA mediates the migration of gastric cancer cells through VEGFR1
Presenter: xiaoxun Wang
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4934 - Risk prediction of metastasis through study of circulating tumor cells
Presenter: Panagiotis Apostolou
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3289 - First step to metastasis: miRNAome abnormalities impair cell-cell adhesion and facilitate detachment of breast cancer cells
Presenter: Volodymyr Halytskiy
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4110 - Extracellular matrix of normal brain tissue is affected by temozolomide during anti-glioblastoma treatment
Presenter: Alexandra Tsidulko
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1526 - Study of the activation of TLR receptors in neurospheres from glioblastoma cells in vitro
Presenter: David Albert Bellver
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4862 - 5-Fluorouracil induced up-regulation of exosomal PD-L1 causing immunosuppression in gastric cancer patients
Presenter: Zhang Min
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
635 - Thrombocytosis and leukocytosis: are they negative prognostic factors in solid tumours?
Presenter: Filip Kohutek
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract