Camrelizumab plus low-dose apatinib and SOX in the first-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma: A single-arm, dose-escalation and expansion study.
Authors: Chen Xiaofeng , Ding Yongbin , Wang Deqiang , Wang Kangxin , Xu Hao , Tang Jie , Li Wei , Fang Yueyu , Sun Hui , Liu Liang , Jiang Qiusheng , Pan Lanlan , Tian Yitong , Wang Rong , Xu Tongpeng , Meng Lijuan , Li Fengyuan , Shu Yongqian 
Published: June 2022

e16053

Background: The combination of camrelizumab, an anti-PD-1 monoclonal antibody, and apatinib, a selective VEGFR-2 inhibitor, has shown synergistic antitumor effects in G/GEJ adenocarcinoma patients. We aimed to evaluate the safety and efficacy of camrelizumab combined with low-dose apatinib and SOX in the first-line treatment of advanced G/GEJ adenocarcinoma. Methods: In this study (ChiCTR2000034109), eligible patients were diagnosed as unresectable or potentially resectable G/GEJ adenocarcinoma, HER2-negative or unknown HER2 status, and treatment-naive with inhibitors of VEGFR or PD-1/PD-L1. In dose escalation phase, 9 patients (3 in each group) were given with camrelizumab (200 mg, d1), apatinib (250 mg, qod/qd), and SOX regimen (oxaliplatin, 100/130 mg/m2, d1; S-1, 40 mg, bid, d1-14) every 3 weeks. Afterwards, the optimal combination integrated with safety and efficacy would be applied in dose expansion phase for another 33 patients. After up to 6-8 cycles of quadruple therapy, patients with complete response (CR)/partial response (PR)/stable disease (SD) would continue camrelizumab plus apatinib therapy until disease progression, intolerable toxicities, physician/patient withdrawal, or up to 2 years of camrelizumab therapy. The safety and efficacy were assessed by investigators per CTCAE v5.0 and RECIST v1.1, respectively. The primary endpoints were maximum tolerated dose and objective response rate (ORR). Results: From Jun 12, 2020 to Jul 26, 2021, no patient reported any dose-limiting toxicity in the dose escalation phase, thus another 11 eligible patients had been enrolled to receive quadruple therapy with apatinib (250 mg, qd) and oxaliplatin (130 mg/m2, d1). The patients were characterized with a median age of 59 years (range, 46-57), 30% GEJ adenocarcinoma, 100% lymph node metastasis, and 45% liver metastases. As of Nov 30, 2021, with a median follow-up of 10.9 months (range, 4.2-17.6), safety and efficacy were assessed in 19 evaluable patients, with overall response of 18 PR and 1 SD. Confirmed ORR and DCR were 94.7% (95% CI, 71.9%-99.7%) and 100% (95% CI, 79.1%-100%), respectively. The median PFS, median DOR and estimated 1-year OS rate were 8.3 months (95% CI, 6.1-10.5), 6.7 months (95% CI, 5.9-7.5) and 59.0%, respectively, with the median OS not reached yet. Conversion surgery had been conducted in 2/19 (10.5%) patients, with one case of pathological CR and one clinical CR. Grade 3-4 treatment-related adverse events occurred in 45% of patients, with rash ranking the most frequent. No new safety signal was identified. Conclusions: Camrelizumab combined with low-dose apatinib and SOX showed high level of safety and efficacy in the first-line treatment of advanced G/GEJ adenocarcinoma. Clinical trial information: ChiCTR2000034109.