Abstract 1300P
Background
Platinum-based doublet chemotherapy in combination with immune checkpoint inhibitors is the standard of care for patients with advanced non-small cell lung cancer (NSCLC). The purpose of our study is to explore a new way without chemotherapy by consolidating the efficacy of checkpoint inhibitors in combination with anti-angiogenic agents. AK104, a bispecific antibody, is capable of simultaneously binding PD-1 and CTLA-4 with high affinity. Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor, thereby exerting inhibitory effects on tumor growth and angiogenesis, and has been approved for third-line treatment of NSCLC in China.
Methods
This is a single-arm, two part, phase Ib/II study. All patients were stage IIIB/C or IV NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Part 1 enrolled treatment-naïve patients with advanced NSCLC. Patients will receive AK104 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks, and 12mg anlotinib 2 weeks on/1 week off. Part 2 enrolled patients with metastatic or recurrent NSCLC after progression on treatment with PD-1/PD-L1 inhibitors. Tumor tissues for determination of PD-L1 expression are needed before study treatment. The primary endpoints are objective response rate (ORR) per RECISTv1.1 and safety.
Results
18 treatment-naïve patients (median age was 66 [range:33–73] years old, ECOG performance status 0/1 [11%/89%], male/female [94%/6%], squamous/non-squamous [50%/50%]) with PD-L1 tumor proportion score (TPS) ≥1% were enrolled and received combination therapy (2 received 10 mg/kg AK104, 16 received 15 mg/kg AK104; and all received 12 mg anlotinib) in part 1. At data cut-off (April 15, 2021), in 8 evaluable patients, the ORR was 62.5% (5/8) and DCR was 100% (8/8). Among them, the ORR was 80% (4/5) in non-squamous NSCLC. Grade 3 treatment-related adverse events (TRAEs) occurred in 6% (1/18, 1 proteinuria) of patients. No Grade 4 or 5 TRAEs had occurred.
Conclusions
AK104 in combination with anlotinib showed favorable antitumor activity and an acceptable safety profile in treatment-naïve patients with PD-L1 TPS≥1% NSCLC. This new combination therapy warrants further evaluation for the treatment of NSCLC.
Clinical trial identification
NCT04646330.
Editorial acknowledgement
Legal entity responsible for the study
Akeso Biopharma Co., Ltd.
Funding
Akeso Biopharma Co., Ltd.
Disclosure
W. Song: Financial Interests, Institutional, Sponsor/Funding: Akeso Biopharma, Inc. B. Li: Financial Interests, Institutional, Sponsor/Funding: Akeso Biopharma Co., Ltd. Z.M. Wang: Financial Interests, Personal and Institutional, Sponsor/Funding: Akeso Biopharma Co., Ltd. Y. Xia: Financial Interests, Institutional, Sponsor/Funding: Akeso Biopharma Co., Ltd. All other authors have declared no conflicts of interest.