Reference Detail

Ref Type

Abstract

PMID

Authors

L. Wu B. Chen W. Yao X. Li Z. Xiao H. Liu Y. Kong L. Liu Y. Xu Q. Wang J. Li F. Xu L. Xu K. Li W. Song B. Li Z.M. Wang Y. Xia

Title

A phase Ib/II trial of AK104 (PD-1/CTLA-4 bispecific antibody) in combination with anlotinib in advanced NSCLC

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	32		September 01, 2021

URL

https://www.annalsofoncology.org/article/S0923-7534(21)04132-6/fulltext

Abstract Text

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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CD274 positive	lung non-small cell carcinoma	predicted - sensitive	Anlotinib + Cadonilimab	Phase Ib/II	Actionable	In a Phase Ib/II trial, combination treatment with Cadonilimab and Anlotinib (AL-3818) demonstrated antitumor activity in patients with CD274 (PD-L1) positive (TPS >= 1%) non-small cell lung cancer, and led to an objective response rate of 62.5% (5/8) and a disease control rate of 100% (8/8). (Annals of Oncology 32 (2021): S1006; NCT04646330).	detail...