Abstract 3930
Background
Tepotinib is an oral, selective, potent MET tyrosine kinase inhibitor, with promising clinical activity in patients (pts) with MET+ tumors, being tested in NSCLC harboring METex14 mutations or MET amplification. We aimed to further characterize the safety profile of tepotinib.
Methods
Safety data from pts receiving tepotinib 500 mg once daily (QD) from five studies (NCT01014936, NCT01832506, NCT01988493, NCT02115373, NCT02864992) were pooled and summarized. Pts received tepotinib until disease progression, intolerable toxicity, or other withdrawal. Adverse events (AEs) were graded by NCI CTCAE v4.03.
Results
As of 9/28/2018, 422 pts had received tepotinib; 228 received 500 mg tepotinib monotherapy QD and were further analyzed for safety (73.2% male, 50.9%/35.5% white/Asian, median age 65.0 [range 19–89] yrs). Median treatment duration was 2.7 months (range 0.0–21.5); in NSCLC pts with METex14 mutations it was 4.1 months (NCT02864992). 219 pts (96.1%) had an AE (any cause). 122 pts (53.5%) had a Grade ≥3 any cause AE including (>3.5%): disease progression (n = 18, 7.9%), hyponatremia (n = 12, 5.3%), increased aspartate aminotransferase (AST) (n = 12, 5.3%), increased lipase (n = 11, 4.8%), peripheral edema (n = 9, 3.9%) and ascites (n = 9, 3.9%). The incidence rates were: 19.0, 12.9, 12.9, 12.0, 9.6 and 9.6 per 100 pt-years, respectively. Treatment-related (TR)AEs are shown in the Table. 18 pts (7.9%) had a serious TRAE including (≥1%) peripheral edema (n = 4, 1.8%). AEs (any cause) led to dose reduction of tepotinib in 33 pts (14.5%) and discontinuation in 49 pts (21.5%), and was due to peripheral edema in 5 (8.5%) and 7 (3.1%) pts, respectively. Of 25 AEs leading to death, two were considered treatment related by the investigator (upper GI hemorrhage and hypoglycemic coma).
Conclusions
Tepotinib demonstrated an acceptable safety profile across a range of tumor types and is being developed in NSCLC as monotherapy and in combination. Further characterization of peripheral edema is ongoing.Table:
479P
N = 228 | ||
---|---|---|
Any Grade (≥10%) | Grade ≥3 (≥2%) | |
Any TRAE, n (%) | 172 (75.4) | 52 (22.8) |
Peripheral edema | 77 (33.8) | 8 (3.5) |
Diarrhea | 45 (19.7) | 4 (1.8) |
Fatigue | 34 (14.9) | 3 (1.3) |
Nausea | 29 (12.7) | 0 (0) |
Decreased appetite | 27 (11.8) | 0 (0) |
Increased lipase | 13 (5.7) | 9 (3.9) |
Increased AST | 11 (4.8) | 5 (2.2) |
Clinical trial identification
NCT01014936, NCT01832506, NCT01988493, NCT02115373, NCT02864992.
Editorial acknowledgement
Medical writing assistance (funded by Merck Healthcare KGaA, Darmstadt, Germany) was provided by Matthew deSchoolmeester, PhD of Bioscript Science (Macclesfield, UK).
Legal entity responsible for the study
Merck KGaA.
Funding
Merck KGaA.
Disclosure
T. Decaens: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: IPSEN; Honoraria (self), Travel / Accommodation / Expenses: Gilead; Honoraria (self), Travel / Accommodation / Expenses: Abbvie; Honoraria (self): Sanofi; Advisory / Consultancy: SITEX; Research grant / Funding (institution): ArQule; Research grant / Funding (institution): Genoscience Pharma; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy: BTG; Advisory / Consultancy: Sirtex. R. Veillon: Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Merck. K. Yamazaki: Honoraria (self): Chugai; Honoraria (self): Takeda; Honoraria (self): Yakult; Honoraria (self): Daiichi‐sankyo; Honoraria (self): Merck Serono; Honoraria (self): Bristol; Honoraria (self): Bayer; Honoraria (self): Eli Lilly; Honoraria (self): Taiho; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi. J. Scheele: Full / Part-time employment: Merck KGaA. R. Bruns: Full / Part-time employment: Merck KGaA. K. Berghoff: Full / Part-time employment: Merck KGaA. S. Faivre: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Blueprint; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer Pharma; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Eli Lilly; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis. P.P. Paik: Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Abbvie; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono; Honoraria (self): Takeda. All other authors have declared no conflicts of interest.
Resources from the same session
5995 - Invasive fungal diseases caused by rare pathogens in patients after hematopoietic stem cell transplantation (HSCT) & chemotherapy
Presenter: Yuliya Rogacheva
Session: Poster Display session 1
Resources:
Abstract
2961 - Safety and pharmacokinetics of novel CXCR4 antagonist YF-H-2015005 in the mobilization of hematopoietic stem cells in patients with non-Hodgkin's lymphoma
Presenter: Weiping Liu
Session: Poster Display session 1
Resources:
Abstract
5771 - Chemotherapy associated Hyponatremia in Hematological Malignancies: A retrospective study of 189 patients treated in a single medical center
Presenter: Vadim Lesan
Session: Poster Display session 1
Resources:
Abstract
1165 - Risk factors for Bacteremia-Associated Mortality of Aeromona sobria in Hematologic Malignancies
Presenter: Gabriel De la Cruz-Kú
Session: Poster Display session 1
Resources:
Abstract
5287 - Use of droplet digital polymerase chain reaction for detecting minimal residual disease: a prospective, multi-institutional study
Presenter: Hyunkyung Park
Session: Poster Display session 1
Resources:
Abstract
1886 - RUBIH2 — Use of NGS in haematological malignancies: from real world data to national recommendations, an innovative program to evaluate the impact of healthcare technology on patient care
Presenter: Severine Coquerelle
Session: Poster Display session 1
Resources:
Abstract
1940 - Outcomes of chronic myeloid leukemia with T315I mutation in the absence of targeted therapy or hematopoietic stem cell transplantation
Presenter: Nageswara Palukuri
Session: Poster Display session 1
Resources:
Abstract
1946 - Is bone marrow examination indispensible in chronic myeloid Leukemia at diagnosis ?
Presenter: Nageswara Palukuri
Session: Poster Display session 1
Resources:
Abstract
1904 - Incidence of Imatinib Resistance in Chronic Myeloid Leukemia (CML) Patients: Experience from Resource Poor Centre of Eastern India
Presenter: Debmalya Bhattacharyya
Session: Poster Display session 1
Resources:
Abstract
3245 - BCR-ABL transcript variant’s significance in chronic myeloid leukemia in chronic phase: Institutional experience from a developing country
Presenter: Siva Prasad
Session: Poster Display session 1
Resources:
Abstract