Efficacy and Biomarker Analysis of Camrelizumab in Combination with Apatinib in Patients with Advanced Nonsquamous NSCLC Previously Treated with Chemotherapy.

Abstract

PURPOSE:

Our preclinical work suggests that appropriate angiogenesis inhibition could potentiate PD-1/PD-L1 blockade via alleviating hypoxia, increasing infiltration of CD8+ T cells and reducing recruitment of tumor-associated macrophages. We hereby conducted a clinical trial to evaluate this combination in pretreated patients with advanced non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS:

The study included phase Ib apatinib dose-escalation and phase II expansion cohorts. Patients received apatinib at doses of 250-500 mg orally once daily, in combination with camrelizumab 200 mg intravenously every 2 weeks.

RESULTS:

From March 2017 to October 2018, 105 chemotherapy-pretreated patients with nonsquamous NSCLC were enrolled and received apatinib 250 mg (recommended phase II dose) and camrelizumab. Among them, one (1.0%) complete response, 28 (26.7%) partial responses, and 48 (45.7%) stable diseases were observed. In the efficacy-evaluable population (n = 94), objective response rate (ORR) was 30.9% [95% confidence interval (CI), 21.7-41.2]. The median progression-free survival was 5.7 months (95% CI, 4.5-8.8) and overall survival was 15.5 months (95% CI, 10.9-24.5). Efficacy of combination therapy was evident across all PD-L1 and tumor mutation burden subgroups, and appeared to be improved in patients with STK11/KEAP1 mutation (mutant vs. wild-type, ORR: 42.9% vs. 28.1%; 1-year survival rate: 85.1% vs. 53.1%). No unexpected adverse events were observed.

CONCLUSIONS:

Combined apatinib and camrelizumab showed encouraging antitumor activity and acceptable toxicity in chemotherapy-pretreated patients with advanced nonsquamous NSCLC. Patients with STK11/KEAP1 mutation might derive more benefits from this combination. We will validate these results in an ongoing phase III trial (NCT04203485).

• Authors: Caicun Zhou, Yina Wang, Jun Zhao, Gongyan Chen, Zhihua Liu, Kangsheng Gu, Meijuan Huang, Jianxing He, Jianhua Chen, Zhiyong Ma, Jifeng Feng, Jianhua Shi, Xinmin Yu, Ying Cheng, Yu Yao, Yuan Chen, Renhua Guo, Xiaoyan Lin, Zhehai Wang, Guanghui Gao, Quanren Wang, Weixia Li, Xinfeng Yang, Lihong Wu, Jun Zhang, Shengxiang Ren
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 27 Issue 5 Pg. 1296-1304 (03 01 2021) ISSN: 1557-3265 [Electronic] United States
• PMID: 33323401 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal, Humanized
• Biomarkers, Tumor
• Pyridines
• apatinib
• camrelizumab

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (metabolism)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, pathology)
• Case-Control Studies
• Female
• Follow-Up Studies
• Humans
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Male
• Middle Aged
• Prognosis
• Pyridines (administration & dosage)
• Retrospective Studies
• Survival Rate
• Young Adult