Efficacy and safety of anlotinib plus penpulimab as second-line treatment for small cell lung cancer: A multicenter, open-label, single-arm phase II trial

• Published in: Cancer pathogenesis and therapy Vol. 2; no. 4; pp. 268 - 275
• Main Authors: Zhang, Changgong, Chen, Jianhua, Wu, Huijuan, Wang, Jun, Gao, Liying, Zhao, Jun, Sun, Yan, Jia, Zhongyao, Mu, Xinlin, Bai, Chunmei, Wang, Rui, Wu, Kailiang, Liu, Qiang, Shi, Yuankai
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2024; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China%Department I of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410083, China%Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China%Department II of Head and Neck Tumor, Gansu Provincial Cancer Hospital, Lanzhou, Gansu 730050, China%Department III of Radiotherapy, Gansu Provincial Cancer Hospital, Lanzhou, Gansu 730050, China%Department I of Thoracic Oncology, Beijing Cancer Hospital, Beijing 100142, China%Department of Oncology, Linyi People's Hospital, Linyi, Shandong 276002, China%Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing 100032, China%Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China%Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China%Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai 200030, China%Department I of Oncology, Shenyang Chest Hospital, Shenyang, Liaoning 110044, China; Elsevier
• Subjects: Anlotinib; Efficacy; Penpulimab; Phase II trial; Safety; Small cell lung cancer; Efficacy; Anlotinib; Small cell lung cancer; Penpulimab; Safety; Phase II trial
• ISSN: 2949-7132; 2097-2563; 2949-7132
• DOI: 10.1016/j.cpt.2024.02.001

Currently, the need for new therapeutic strategies involving programmed cell death protein-1 (PD-1) monoclonal antibodies in the second-line setting of small cell lung cancer (SCLC) is urgent. This study aimed to evaluate the efficacy and safety of anlotinib plus penpulimab as a second-line treatment for patients with SCLC who progressed after first-line platinum-based chemotherapy. This study included the patients from Cohort 4 of a single-arm, open-label, multicenter, phase II clinical trial. A safety run-in phase was performed under anlotinib (10/12 mg quaque die [QD], days 1–14) plus penpulimab (200 mg intravenously [IV], day 1) in a 21-day cycle, followed by the formal trial in which the patients received anlotinib (12 mg QD, days 1–14) plus penpulimab (200 mg IV, day 1) in a 21-day cycle. The primary endpoint of the safety run-in phase was safety. The primary endpoint of the formal trial phase was the objective response rate (ORR). From April 28, 2020, to November 24, 2020, 21 patients were enrolled from 11 hospitals, including 2 in the safety run-in phase and 19 in the formal trial phase. In the formal trial phase, the ORR was 42.1% (8/19; 95% confidence interval [CI]: 17.7–66.6%). The median progression-free survival was 4.8 months (95% CI: 2.9–11.3 months), and the median overall survival was 13.0 months (95% CI: 4.6–not applicable [NA] months). The incidence of ≥grade 3 treatment-related adverse events (TRAEs) was 52.4% (11/21), and the incidence of treatment-related serious adverse events (AEs) was 28.6% (6/21). Two AE-related deaths occurred. The most common AEs were hypertension (57.1%, 12/21), hypothyroidism (42.9%, 9/21), and hypertriglyceridemia (38.1%, 8/21). In patients with SCLC who progressed after first-line platinum-based chemotherapy, the second-line anlotinib plus penpulimab treatment demonstrates promising anti-cancer activity and a manageable safety profile, which warrants further investigation. No. NCT04203719, https://clinicaltrials.gov/. [Display omitted] •Anlotinib plus penpulimab shows promising anti-cancer activity and acceptable safety profile in the 2nd-line treatment of small cell lung cancer (SCLC).•Patients who underwent the anlotinib plus penpulimab regimen had an objective response rate (ORR) of up to 42.1% (95% confidence interval [CI]: 17.7–66.6%), a median progression-free survival (PFS) of 4.8 months (95% CI: 2.9–11.3 months), and a median overall survival (OS) of 13.0 months (95% CI: 4.6–not applicable [NA] months).•The anlotinib plus penpulimab regimen warrants further investigation for the treatment of patients with stage SCLC who progressed after first-line platinum-based chemotherapy.