Phase II trial of efficacy, safety and biomarker analysis of sintilimab plus anlotinib for patients with recurrent or advanced endometrial cancer.

Abstract

BACKGROUND:

Although co-inhibition of the angiogenesis and programmed death 1 (PD-1) pathways is proposed as an effective anticancer strategy, studies in Chinese patients with endometrial cancer are sufficient. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor affecting tumor angiogenesis and proliferation; sintilimab is an anti-PD-1 monoclonal antibody.

METHODS:

This was a phase II trial using Simon's two-stage design. This study enrolled patients with endometrial cancer who had progressed after platinum-based chemotherapy. Sintilimab 200 mg was administered intravenously on day 1 every 3 weeks, and anlotinib 12 mg was administered on days 1-14 in a 21-day cycle. The primary endpoint was the objective response rate (ORR) using the immune-related Response Evaluation Criteria in Solid Tumors criteria. Immunohistochemistry and whole-exome sequencing were used as correlative investigations.

RESULTS:

Between November 2019 and September 2020, 23 eligible patients were enrolled. The ORR and disease control rates were 73.9% (95% CI, 51.6 to 89.8) and 91.3% (95% CI, 72.0 to 98.9), respectively, with 4 complete and 12 partial responses. With a median follow-up of 15.4 months (95% CI, 12.6 to 18.3), the median progression-free survival was not reached, and the probability of PFS >12 months was 57.1% (95% CI, 33.6 to 75.0). Exploratory analysis revealed that mutations in the homologous repair pathway showed a trend for higher ORR (100% vs 0%, p=0.07). Treatment-related grade 3/4 adverse events were observed in 50.0% of the patients.

CONCLUSIONS:

Sintilimab plus anlotinib demonstrated robust therapeutic benefits with tolerable toxicity in endometrial cancer.

TRIAL REGISTRATION NUMBER:

NCT04157491.

• Authors: Wei Wei, Xiaohua Ban, Fan Yang, Jibin Li, Xiaqin Cheng, Rong Zhang, Xin Huang, Yongwen Huang, Qiaqia Li, Ya Qiu, Min Zheng, Xiaofeng Zhu, Jundong Li
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 10 Issue 5 (05 2022) ISSN: 2051-1426 [Electronic] England
• PMID: 35623659 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Antibodies, Monoclonal, Humanized
• Biomarkers
• Indoles
• Quinolines
• anlotinib
• sintilimab

Topics

• Antibodies, Monoclonal, Humanized
• Biomarkers
• Endometrial Neoplasms (drug therapy)
• Female
• Humans
• Indoles
• Quinolines (pharmacology, therapeutic use)