Camrelizumab combined with apatinib and S-1 as second-line treatment for patients with advanced gastric or gastroesophageal junction adenocarcinoma: a phase 2, single-arm, prospective study.

Abstract

BACKGROUND:

The current second-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma remains unsatisfactory. Anti-PD-1 monoclonal antibody combined with anti-angiogenic therapy shows anti-tumor activity and synergistic effect. We aimed to assess the efficacy and safety of the combination therapy of camrelizumab, apatinib, and S-1 in patients with gastric or gastroesophageal junction adenocarcinoma.

METHODS:

In this open-label, single-arm, phase 2 trial, in each 21-day cycle, eligible patients received 200 mg intravenous camrelizumab in the first day, 500 mg oral apatinib once daily continuously, and specific dose oral S-1 in the first 14 days until the trial was discontinued disease progression, development of intolerable toxicity, or withdrawal of consent. The primary endpoint was objective response rate. The secondary endpoints were disease control rate, progression-free survival and overall survival, and safety. This study was registered at ClinicalTrials.gov, NCT04345783.

RESULTS:

Between May 2019 and August 2020, we enrolled a total of 24 patients in this trial. At the data cutoff (December 1, 2020), the median follow-up duration was 8.13 months. Seven of 24 (29.2%, 95%CI 14.9-49.2%) patients reached objective response. The median-progression-free survival was 6.5 months (95%CI 6.01-6.99) and the median overall survival was not reached. Grade 3 or 4 adverse events occurred in 6 (25.0%) patients, including elevated transaminase, thrombocytopenia, fatigue, proteinuria, and intestinal obstruction. No serious treatment-related adverse events or treatment-related deaths occurred.

CONCLUSIONS:

In this trial, the combination of camrelizumab, apatinib, and S-1 showed promising anti-tumor activity and manageable toxicity as a second-line therapy in patients with advanced gastric or gastroesophageal junction adenocarcinoma, regardless of PD-L1 expression.

CLINICAL TRIAL REGISTRATION:

NCT04345783.

• Authors: Chao Jing, Junyun Wang, Mingyue Zhu, Zhigang Bai, Baoyi Zhao, Jun Zhang, Jie Yin, Xiaobao Yang, Zongzhi Liu, Zhongtao Zhang, Wei Deng
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 71 Issue 11 Pg. 2597-2608 (Nov 2022) ISSN: 1432-0851 [Electronic] Germany
• PMID: 35304622 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen
• Pyridines
• apatinib
• camrelizumab
• Transaminases

Topics

• Adenocarcinoma (drug therapy, pathology)
• Antibodies, Monoclonal, Humanized (adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• B7-H1 Antigen (therapeutic use)
• Esophageal Neoplasms
• Esophagogastric Junction (pathology)
• Humans
• Prospective Studies
• Pyridines
• Transaminases (therapeutic use)