Randomized phase III ANGEL study of rivoceranib (apatinib) plus best supportive care (BSC) vs placebo plus BSC in patients with advanced/metastatic gastric cancer who failed >= 2 prior chemotherapy regimens

Abstract Background Rivoceranib is an oral, selective tyrosine kinase inhibitor of VEGFR-2 with demonstrated efficacy for gastric cancer in China. ANGEL was a global phase III study to evaluate the efficacy and safety of rivoceranib in gastric cancer. Methods Main eligibility criteria included advanced/metastatic adenocarcinoma of the stomach or gastroesophageal junction after failure of ≥ 2 prior lines of chemotherapy; ECOG PS ≤ 1. Patients were stratified by geographic region (Asia vs North America/Europe), disease measurability, prior ramucirumab use, and treatment therapy line (3rd or ≥ 4th), and randomized (2:1 ratio) to rivoceranib 700 mg qd po or matched placebo with BSC until disease progression, intolerable toxicity or withdrawal of consent. Primary endpoint: overall survival (OS, ITT population). Secondary endpoints: progression-free survival (PFS); objective response rate (ORR); disease control rate (DCR); quality of life (QoL); safety. Clinical trial registration: NCT03042611. Results Overall, 460 patients (rivoceranib n = 308, placebo n = 152) were enrolled from Feb 2017 – Oct 2018. Baseline demographics were balanced. While mOS in ≥ 3rd-line patients did not show statistical difference for rivoceranib vs placebo (5.78 vs 5.13 mo; HR = 0.93; 95% CI 0.74–1.15; p = 0.4850), mPFS was significantly improved with rivoceranib (2.83 vs 1.77 mo; HR = 0.57; 95% CI 0.46–0.79; p Conclusions While OS was not significantly improved in the overall population, most other efficacy endpoints including OS in ≥ 4th-line suggest that rivoceranib has a benefit and is well tolerated in patients with gastric cancer. Clinical trial identification NCT03042611. Editorial acknowledgement Lee Miller, Miller Medical Communications Ltd. Legal entity responsible for the study LSK BioPharma. Funding LSK BioPharma. Disclosure Y. Kang: Advisory / Consultancy: ONO; Advisory / Consultancy: BMS; Advisory / Consultancy: Daehwa; Advisory / Consultancy: LSK Biopharma; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Macrogenics; Advisory / Consultancy: Zymeworks; Advisory / Consultancy: Blueprint; Advisory / Consultancy: Merck Serono; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Astellas; Research grant / Funding (institution): Roche. M. Di Bartolomeo: Honoraria (self), Speaker Bureau / Expert testimony: Lilly spa; Honoraria (self), Speaker Bureau / Expert testimony: Servier; Honoraria (self), Speaker Bureau / Expert testimony: Merck-Serono; Honoraria (self), Speaker Bureau / Expert testimony: MSD; Travel / Accommodation / Expenses: Roche spa; Travel / Accommodation / Expenses: Sanofi. I. Chau: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eli-Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: MSD; Advisory / Consultancy: Bayer; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck-Serono; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Oncologie International; Advisory / Consultancy: Pierre Fabre; Research grant / Funding (institution): Janssen-Cilag; Research grant / Funding (institution): Sanofi Oncology. H.H. Yoon: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): LSK; Honoraria (institution), Advisory / Consultancy: BeiGene; Advisory / Consultancy: FivePrime Therapeutics; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Merrimack; Research grant / Funding (institution): Genetech/Roche; Research grant / Funding (institution): Boston Biomedical. S. Cascinu: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly. M. Ryu: Honoraria (self), Advisory / Consultancy: ONO; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Taiho; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Daehwa. K. Lee: Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self): Eli Lilly; Research grant / Funding (institution): ALX Oncology; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): ASLAN Pharmaceuticals; Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): Green Cross Corp.; Research grant / Funding (institution): LSK BioPharma; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Merck KGaA; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Pharmacyclics. A. McGinn: Shareholder / Stockholder / Stock options, Full / Part-time employment: LSK BioPharma. N. Sankar: Shareholder / Stockholder / Stock options, Full / Part-time employment: LSK BioPharma. N. Boku: Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self): Eli Lilly; Honoraria (self): Chugai. All other authors have declared no conflicts of interest.