A phase I multiple-dose escalation study to assess the safety, tolerability, and pharmacokinetics of VEGF-receptor inhibitor telatinib (EOC315) in Chinese patients with advanced solid tumors.

Authors

null

Hongming Pan

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

Hongming Pan , Tianshu Liu , Jason Tsai , Yapeng Zhao

Organizations

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China, Zhongshan Hospital, Fudan University, Shanghai, China, EOC Pharma, Shanghai, China

Research Funding

Pharmaceutical/Biotech Company

Background: Telatinib (EOC315) is a highly selective inhibitor of VEGFR/PDGFR (VEGFR 1-3, PDGFR-β, and c-Kit tyrosine kinases). This phase I study was to assess the safety, tolerability, and pharmacokinetics (PK) of Telatinib in Chinese patients with advanced solid tumors. Methods: Telatinib was administered to Chinese patients with advanced refractory solid tumors as a single agent in 3+3 dose escalation design, starting from 600mg and escalated to 900mg and 1200mg, given orally twice daily. The PK profile, safety, and tolerability were evaluated per protocol. Efficacy was evaluated with RECIST 1.1 criteria every 6 weeks. Results: A total of 15 subjects (6 colorectal cancer, 4 lung cancer, 1 head and neck cancer, 1 melanoma, 1 thymic carcinoma, 1 esophageal carcinoma,1 peritoneal carcinoma) were enrolled per protocol between July 2017 and August 2018, and 13 subjects received at least second line therapies before enrollment. Telatinib was well tolerated in the three dose arms. No dose limiting toxicities (DLTs) occurred during the dose escalation phase. CTC grade 3 AEs observed include hypertension (46.7%, 7/15), fatigue (6.7%, 1/15), transaminase elevation (6.7%, 1/15), hand-foot syndrome (6.7%, 1/15), oral mucositis (6.7%, 1/15), neutropenia (6.7%, 1/15), urobilinogen elevation (6.7%, 1/15), left ventricular systolic dysfunction/decreased ejection fraction (6.7%, 1/15). No CTC grade 4 AE were observed. There were 2 drug related SAEs (hospitalization due to high blood pressure. The PK profile of Telatinib (EOC315) at 600, 900, 1200 mg in Chinese patient cohorts is summarized in Table. For 12 evaluable patients, DCR was 58.3%. For all patients, mPFS was 15 weeks (3.3-34.3w). Conclusions: This study demonstrated the safety and tolerability of Telatinib (EOC315) in a multiple dose escalation design at 600, 900, and 1200 mg PO bid in Chinese patients with advanced refractory solid tumor. Telatinib AUC increased dose-proportionally from 600 mg to 900 mg bid, where 900 mg Telatinib bid is the maximum feasible and recommended dose for future studies in Chinese patients with advanced tumors. Clinical trial information: NCT03175497

Telatinib multiple does pharmacokinetic parameters (D14).

Dose
(mg)
t1/2 (h)AUC0-12h
(h*ng/mL)
Vz/F
(L)
CLss/F
(L/h)
RAUC0-12h
600 (N=3)6.20±2.365309.36±3661.961259.21±828.99146.25±72.371.63±1.13
900 (N=3+6)3.90±1.819708.02±2687.77543.42±145.2799.00±27.581.17±0.74
1200 (N=3)7.987243.44±2776.602723.15181.06±61.050.78±0.39

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics and Tumor Biology (Nonimmuno)

Track

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Sub Track

Conduct of Clinical Research

Clinical Trial Registration Number

NCT03175497

Citation

J Clin Oncol 37, 2019 (suppl; abstr 3061)

DOI

10.1200/JCO.2019.37.15_suppl.3061

Abstract #

3061

Poster Bd #

53

Abstract Disclosures