Rivoceranib, a VEGFR-2 inhibitor, monotherapy in previously treated patients with advanced or metastatic gastric or gastroesophageal junction cancer (ANGEL study): an international, randomized, placebo-controlled, phase 3 trial.

"Declarations Conflict of interestYoon-Koo Kang declares consulting fees from Amgen, Novartis, Roche, Daehwa, Zymeworks, Blueprint, Surface Oncology, ALX Oncology, Macrogenics, BMS, Merck. Min-Hee Ryu declares support for the present manuscript from Elevar Therapeutics; consulting fees from Bristol Meyers Squibb, Ono Pharmaceutical, MSD, Lilly, Novartis, Taiho, AstraZeneca, Daiichi Sankyo; payment or honoraria from Bristol Meyers Squibb, Ono Pharmaceutical, MSD, Lilly, Novartis, Taiho, AstraZeneca, Daiichi Sankyo. Maria Di Bartolomeo declares no conflicts of interests. Ian Chau declares advisory board participation for Eli-Lilly, Bristol Meyers Squibb, MSD, Roche, Merck-Serono, Astra-Zeneca, OncXerna, Pierre Fabre, Boehringer Ingelheim, Incyte, Astella, GSK, Sotio, Eisai, Daiichi-Sankyo, Taiho, Servier, Seagen, Turning Point Therapeutics, Novartis; research funding from Eli-Lilly and Janssen-Cilag; honoraria from Eli-Lilly, Eisai, Servier, and Roche. Harry Yoon declares honoraria from Astellas, Elevation Oncology, MJH Life Sciences, and PRIME; consulting or advisory role for ALX Oncology, Amgen, AstraZeneca, BeiGene, Bristol Myer Squibb, Macrogenics, Merck, Novartis, OncXerna, and Zymeworks; expert testimony for MJH Life Sciences; travel/accommodations/expenses from Astellas, BeiGene, Elevation Oncology, and PRIME. Jong Gwang Kim declares no conflicts of interest. Keun-Wook Lee declares support for the present manuscript from Elevar Therapeutics; grants/contracts from AstraZeneca, Ono Pharmaceutical, Merck Sharp and Dohme, Merck KGaA, Pfizer, Beigene, Zymeworks, ALX Oncology, Astellas, Macrogenics, Five Prime Therapeutics, SEagen, Bolt Therapeutics, Trishula Therapeutics, Oncologie, Pharmacyclics, MedPacto, Green Cross Corp, ABLBIO, Y-BIOLOGICS, Genexine, Daiichi Sankyo, Taiho Pharmaceutical, InventisBio, Leap Therapeutics; honoraria from Ono Pharmacuetical and Boryung; participation on a data safety monitoring board of advisory board for ALX Oncology. Sang Cheul Oh declares no conflicts of interest. Atsuo Takashima declares grants/contracts from Daiichi Sankyo, Ono Pharmaceutical, Bristol-Myers Squibb, Hutchison Media Pharma, Pfizer, Merck Sharp & Dohme, Isofol Medical AB, Incyte Corporation; honoraria from Lilly, Taiho Pharmaceutical, Takeda, Ono Pharmaceutical, Chugai Pharma, Merck Serono. Anna Kryzhanivska declares no conflict of interest. Yee Chao declares support for the present manuscript from Elevar Therapeutics. Ludovic Evesque declares honoraria from Servier, Bristol Meyers Squibb, and MSD. Michael Schenker declares support for the present manuscript from Elevar Therapeutics; grants or contract from AbbVie Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Clovis, Lilly, Gilead, GlaxoSmithKline, Merck, MSD, Mylan, Novartis, Pfizer, Pharma Mar, Regeneron, Roche, Samsung Pharmaceuticals, Serono, Tesaro. Arlo McGinn declares employment and stock options from Elevar Therapeutics. Yufan Zhao declares employment and stock options from Elevar Therapeutics. Jennifer Lee declares former employment with Elevar Therapeutics and a leadership role with Enzyme by Design, How Women Lead. Lucjan Wyrwicz declares investigator fees related to the current study. Narikazu Boku declares research funding from Ono Pharmaceutical and Takeda Pharmaceutical; honoraria from Ono Pharmaceutical, Bristol Meyers Squibb, Eli Lilly, Daiichi-Sankyo, Taiho. Ethical approvalAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consentInformed consent was obtained from all individual participants included in the study. Conflict of interest Yoon-Koo Kang declares consulting fees from Amgen, Novartis, Roche, Daehwa, Zymeworks, Blueprint, Surface Oncology, ALX Oncology, Macrogenics, BMS, Merck. Min-Hee Ryu declares support for the present manuscript from Elevar Therapeutics; consulting fees from Bristol Meyers Squibb, Ono Pharmaceutical, MSD, Lilly, Novartis, Taiho, AstraZeneca, Daiichi Sankyo; payment or honoraria from Bristol Meyers Squibb, Ono Pharmaceutical, MSD, Lilly, Novartis, Taiho, AstraZeneca, Daiichi Sankyo. Maria Di Bartolomeo declares no conflicts of interests. Ian Chau declares advisory board participation for Eli-Lilly, Bristol Meyers Squibb, MSD, Roche, Merck-Serono, Astra-Zeneca, OncXerna, Pierre Fabre, Boehringer Ingelheim, Incyte, Astella, GSK, Sotio, Eisai, Daiichi-Sankyo, Taiho, Servier, Seagen, Turning Point Therapeutics, Novartis; research funding from Eli-Lilly and Janssen-Cilag; honoraria from Eli-Lilly, Eisai, Servier, and Roche. Harry Yoon declares honoraria from Astellas, Elevation Oncology, MJH Life Sciences, and PRIME; consulting or advisory role for ALX Oncology, Amgen, AstraZeneca, BeiGene, Bristol Myer Squibb, Macrogenics, Merck, Novartis, OncXerna, and Zymeworks; expert testimony for MJH Life Sciences; travel/accommodations/expenses from Astellas, BeiGene, Elevation Oncology, and PRIME. Jong Gwang Kim declares no conflicts of interest. Keun-Wook Lee declares support for the present manuscript from Elevar Therapeutics; grants/contracts from AstraZeneca, Ono Pharmaceutical, Merck Sharp and Dohme, Merck KGaA, Pfizer, Beigene, Zymeworks, ALX Oncology, Astellas, Macrogenics, Five Prime Therapeutics, SEagen, Bolt Therapeutics, Trishula Therapeutics, Oncologie, Pharmacyclics, MedPacto, Green Cross Corp, ABLBIO, Y-BIOLOGICS, Genexine, Daiichi Sankyo, Taiho Pharmaceutical, InventisBio, Leap Therapeutics; honoraria from Ono Pharmacuetical and Boryung; participation on a data safety monitoring board of advisory board for ALX Oncology. Sang Cheul Oh declares no conflicts of interest. Atsuo Takashima declares grants/contracts from Daiichi Sankyo, Ono Pharmaceutical, Bristol-Myers Squibb, Hutchison Media Pharma, Pfizer, Merck Sharp & Dohme, Isofol Medical AB, Incyte Corporation; honoraria from Lilly, Taiho Pharmaceutical, Takeda, Ono Pharmaceutical, Chugai Pharma, Merck Serono. Anna Kryzhanivska declares no conflict of interest. Yee Chao declares support for the present manuscript from Elevar Therapeutics. Ludovic Evesque declares honoraria from Servier, Bristol Meyers Squibb, and MSD. Michael Schenker declares support for the present manuscript from Elevar Therapeutics; grants or contract from AbbVie Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Clovis, Lilly, Gilead, GlaxoSmithKline, Merck, MSD, Mylan, Novartis, Pfizer, Pharma Mar, Regeneron, Roche, Samsung Pharmaceuticals, Serono, Tesaro. Arlo McGinn declares employment and stock options from Elevar Therapeutics. Yufan Zhao declares employment and stock options from Elevar Therapeutics. Jennifer Lee declares former employment with Elevar Therapeutics and a leadership role with Enzyme by Design, How Women Lead. Lucjan Wyrwicz declares investigator fees related to the current study. Narikazu Boku declares research funding from Ono Pharmaceutical and Takeda Pharmaceutical; honoraria from Ono Pharmaceutical, Bristol Meyers Squibb, Eli Lilly, Daiichi-Sankyo, Taiho."

"Funding This study was funded by Elevar Therapeutics."

"The ANGEL study (ClinicalTrials.gov registration number: NCT03042611) was a prospective, randomized, double-blinded, placebo-controlled, multicenter, multinational, phase 3 study to evaluate the efficacy and safety of rivoceranib plus BSC versus placebo plus BSC. Patients were enrolled at 95 sites in 12 countries, including the USA, Europe, and Asia."