Safety and efficacy of sintilimab combined with oxaliplatin/capecitabine as first-line treatment in patients with locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma in a phase Ib clinical trial

Haiping Jiang, Yulong Zheng, Jiong Qian, Chenyu Mao, Xin Xu, Ning Li, Cheng Xiao, Huan Wang, Lisong Teng, Hui Zhou, Shuyan Wang, Donglei Zhu, Bo Peng, Lin Shen, Nong Xu, Haiping Jiang, Yulong Zheng, Jiong Qian, Chenyu Mao, Xin Xu, Ning Li, Cheng Xiao, Huan Wang, Lisong Teng, Hui Zhou, Shuyan Wang, Donglei Zhu, Bo Peng, Lin Shen, Nong Xu

Abstract

Background: Sintilimab blocks the interaction between programmed death-1 (PD-1) and its ligands. The safety and efficacy of sintilimab combined with oxaliplatin/capecitabine (CapeOx) as first-line treatment were evaluated in patients with gastric (G)/gastroesophageal junction (GEJ) adenocarcinoma in a phase Ib clinical trial.

Methods: Patients with locally advanced or metastatic G/GEJ adenocarcinoma without previous systemic treatment were enrolled as one cohort of a multi-cohort study. Sintilimab was administered at a dose of 200 mg intravenously (IV) in combination with CapeOx (1000 mg/m2 capecitabine orally, bid, D1-14 and 130 mg/m2 oxaliplatin IV, D1) every 21 days for up to 6 cycles. After combination treatment, patients continued to receive sintilimab (200 mg) at 3 weekly intervals as maintenance therapy until progressive disease (PD), unacceptable toxicity, withdrawal of informed consent, or for up to 24 months. Adverse events (AEs) were monitored to assess safety in terms of their frequency, intensity and causality. The efficacy endpoints included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Tumor mutation burden (TMB) was evaluated for its association with clinical response.

Results: A total of 20 patients were enrolled and received sintilimab plus CapeOx. All patients reported treatment-related AEs (TRAEs). Grade 3-4 TRAEs were found in 11 (55.0%) patients. Seventeen patients obtained partial response and the ORR was 85.0% (95% CI: 62.1-96.8%). Three (15.0%) had stable disease and DCR was 100.0% (95% CI: 83.2-100.0%). As data cutoff of May 1, 2019, the median follow-up was 7.8 months. The median PFS was 7.5 months (95% CI: 6.2-9.4) and median OS had not been reached. The OS rates at 6 months and 12 months were 100.0 and 68.0%. No association was observed between TMB and efficacy.

Conclusions: Sintilimab combined with CapeOx as first-line treatment demonstrated acceptable safety and promising efficacy.

Trial registration: ClinicalTrials.gov, NCT02937116 . Registered 8 October 2016.

Keywords: Capecitabine; Gastric/gastroesophageal junction adenocarcinoma; Oxaliplatin; Sintilimab; Tumor mutation burden.

Conflict of interest statement

Hui Zhou, Shuyan Wang, Donglei Zhu, Bo Peng are the staff of Innovent Biologics, Inc., Suzhou, China Suzhou, China. Lin Shen is the associate editor of BMC Cancer. All remaining authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of the study
Fig. 2
Fig. 2
Evaluation of efficacy and tumor responses. a, Maximum change in tumor size from baseline. Seventeen of 20 patients obtained PR based on the percentage changes of the sum of the maximum diameter of the tumor lesion (range − 28% to − 100%); b, the change of lesion diameters over time from baseline; each line represents the changes in one patient; c, PFS Kaplan-Meier curve; d, OS Kaplan-Meier curve; e, the objective response rate in low and high TMB groups. OS, overall survival; PFS, progression-free survival; PR partial response; SD, stable disease; TMB, tumor mutation burden

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