Penpulimab plus anlotinib as second-line treatment for the small cell lung cancer after failure of platinum-based systemic chemotherapy.
Authors: Changgong Zhang, Sheng Yang, Jianhua Chen, Huijuan Wu, Jun Wang, Yingping Li, Liying Gao, Zhongyao Jia, Yan Sun, Jun Zhao, Xin Lin Mu, Chunmei Bai, Rui Wang, Kailiang Wu, Qiang Liu, Xiaoping Jin, Xiaowen Tan, Yuankai Shi
Journal: Journal of Clinical Oncology (2021)

8568 Background: Combined therapy of an immune checkpoint inhibitor with a targeted anti-angiogenic agent had been proved to be effective for lung cancer. Penpulimab (AK105) was engineered to eliminate FcγR binding and antibody-dependent cell-mediated cytotoxicity (ADCC)/ antibody-dependent celluar phagocytosis (ADCP) completely, where ADCC/ADCP effects could induce T-cell apoptosis and clearance and therefore compromise anti-tumor activity. Penpulimab demonstrated a slower programmed death-1(PD-1) antigen binding off-rate, which resulted in better cellular activity and higher receptor occupancy. Penpulimab also showed numerous contacts with N58 glycosylation on the BC loop of PD-1. These structural differentiations enhance the anti-tumor activity of penpulimab and improve its safety. Anlotinib is a multi-targeted tyrosine kinase inhibitor selective for VEGF receptors 1/2/3, FGF receptors 1-4, PDGF receptors α and β, and c-kit. Anlotinib has been approved by National Medical Products Administration as the treatment for small cell lung cancer (SCLC) patients, who had progressed/relapsed on or after at least two regimens of chemotherapy. Here we report the results of one cohort which received penpulimab plus anlotinib in a Phase II study. Methods: In Cohort 4 of an open-label, multi-center, multi-cohort Phase II study evaluating the efficacy and safety of penpulimab plus anlotinib in pts with advanced head, neck or chest tumors(NCT04203719), the SCLC patients, who failed to platinum-based systemic chemotherapy treatment, received penpulimab (200 mg IV Q3W) and anlotinib (12/10 mg PO 2 weeks on/1 week off). Primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints were disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival. Results: 20 patients (median age was 61 [range:37–75] years old, Eastern Cooperative Oncology Group performance status 0/1 [5%/95%], male/female [65%/35%]) were enrolled and received combination therapy (17 received 12 mg anlotinib, 3 received 10 mg anlotinib; and all received 200 mg penpulimab). At data cut-off (Jan 25, 2021), the confirmed ORR was 50.0% (10/20, 1 complete response and 9 partial response) and DCR was 75.0% (15/20). 9 PFS events (45%) had occurred, and the median PFS was 4.7 months (95% CI: 3.6-not reached). Grade 3 treatment-related adverse events (TRAEs) occurred in 30% (6/20, 2 hypertension, 1 hypertriglyceridaemia, 1 gamma-glutamyltransferase increased, 1 palmar-plantar erythrodysaesthesia syndrome and 1 hyponatraemia) of patients, No Grade 4 or 5 TRAEs had occurred. Conclusions: Penpulimab plus anlotinib showed favorable antitumor activity and an acceptable safety profile in SCLC patients who failed to platinum-based systemic chemotherapy. This new combination therapy warrants further evaluation for the treatment of SCLC. Clinical trial information: NCT04203719.