Abstract 1237P
Background
Rivoceranib is a novel oral tyrosine kinase inhibitor that potently and selectively inhibits VEGFR2. Selective inhibition of VEGFR2 has been shown to enhance the efficacy of chemotherapy.
Methods
This open-label, single-arm, dose-escalation (standard 3+3) phase I study recruited adult pts with advanced gastric or GEJ cancer that progressed during or following 1st-line chemotherapy. Pts received rivoceranib at escalating doses starting with 400 mg daily orally + paclitaxel 80 mg/m2 IV on Day 1, 8, and 15 of each cycle, administered in 4-week cycles. Primary objective was to determine the recommended phase II dose (RP2D). Secondary objectives included assessing the safety and tolerability profile, preliminary efficacy using RECIST v1.1, and characterization of the pharmacokinetic (PK) profile of the combination.
Results
12 pts were enrolled: 6 in dose-level (DL)1 (rivoceranib 400 mg + paclitaxel) and 6 in DL2 (rivoceranib 500 mg + paclitaxel). The median age was 56 yrs; 8 were male, 4 were female; ECOG PS 1 in all pts. 83% of pts had at least 1 dose reduction for adverse events (AEs). All pts had ≥1 AE and 91.7% had a Grade ≥3 AE. The most common (>10%) Grade ≥3 AEs were neutropenia (67%), leukopenia (25%), anemia, peripheral neuropathy, and hypertension (17%, each). Grade ≥3 AEs were more frequent in DL2. There was 1 dose-limiting toxicity at each DL (DL1: Grade 3 oral mucositis; DL2: Grade 3 febrile neutropenia). 6 pts had a partial response (4 in DL1, 2 in DL2) for an objective response rate of 60% and a disease control rate of 100% in 10 patients with measurable disease. The PK of both drugs were not altered when both doses of rivoceranib were administered with paclitaxel, suggesting a lack of drug-drug interaction. Considering the safety profile and efficacy trend, the RP2D was defined as rivoceranib 400 mg + paclitaxel 80 mg/m2.
Conclusions
The combination of rivoceranib + paclitaxel as 2nd-line treatment in pts with advanced gastric or GEJ cancer showed good clinical activity with a manageable safety profile. Based on these data, the combination warrants further investigation.
Clinical trial identification
NCT03707028.
Editorial acknowledgement
Editorial assistance was provided by Mark Phillips, PharmD, of Phillips Gilmore Oncology Communications, Inc, funded by Elevar Therapeutics.
Legal entity responsible for the study
Elevar Therapeutics.
Funding
Elevar Therapeutics.
Disclosure
M.H. Ryu: Financial Interests, Personal, Other, Honoraria and Advisory Role: AstraZeneca, Bristol-Myers Squibb, DAEHWA Pharmaceutical, Daiichi Sankyo, Lilly, MSD, Novartis, Ono Pharmaceutical, Taiho Pharmaceutical. A. Pande: Financial Interests, Personal, Full or part-time Employment: Elevar Therapeutics. J.H. Kim: Financial Interests, Personal, Full or part-time Employment: Elevar Therapeutics. Y. Kang: Financial Interests, Personal, Advisory Board: ALX Oncology, Amgen, Blueprint Medicines, Bristol-Myers Squibb, DAEHWA Pharmaceutical, Macrogenics, Novartis, Surface Oncology, Zymeworks.