3930 - Safety profile of tepotinib in patients with advanced solid tumors: pooled analysis of phase I and II data

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

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.