Suzhou, China, July 10, 2023 - Alphamab Oncology (stock code: 9966.HK) announced that the phase Ⅱ clinical research results of anti- PD-L1/CTLA-4 bispecific antibody KN046 monotherapy in advanced NSCLC were published online in the European Journal of Cancer (EJC) (IF: 8.4001). Professor Caicun Zhou from Shanghai Pulmonary Hospital is the corresponding author of this paper.
Corresponding Author: Caicun Zhou,
First authors: Anwen Xiong, Wei Li, Xingya Li
KN046-201 is an open-label, multi-center, multiple cohorts, single arm study to evaluate the efficacy, safety andtolerability of KN046 in NSCLC. Subjects with NSCLC who had failed from first line platinum-based doublet chemotherapy without PD-(L)1 immune checkpoint blockade were enrolled in cohort A and cohort B. All subjects enrolled will receive KN046 3 mg/kg (Cohort A) and 5mg/kg (Cohort B) Q2W IV administration, respectively. Primary endpoint was objective response rate (ORR) per RECIST version 1.1 by BICR.
All 64 patients were enrolled, 30 and 34 patients were included in the 3 mg/kg (cohort A) and 5 mg/kg (cohort B), respectively. On August 31, 2021, the median follow-up duration was 24.08 months and 19.35 months in the 3 mg/kg and 5 mg/kg cohorts, respectively. BICR-assessed ORRs were 13.3% and 14.7% in the 3 mg/kg and 5 mg/kg cohorts, respectively. Median progression-free survival (PFS) were 3.68 and 3.68 months, while overall survival (OS) were 19.70 and 13.04 months, respectively. Furthermore, the ORR was 17.1%, mPFS was 3.68 months and mOS was 19.81 months in non-squamous NSCLC (n=41). And in squamous NSCLC(n=20), the ORR was 10.0%, mPFS was 7.43 months and mOS was 12.88months.
All 64 enrolled patients were evaluable for safety, the most common treatment-related adverse events (TRAEs) were anemia (28.1%), hyperglycemia (26.7%), and infusion-related reactions (26.7%). The incidence rates of grade ≥3 TRAEs and TRAEs leading to treatment discontinuation were 42.2% and 14.1%, respectively.
Conclusion: Both 3 mg/kg and 5 mg/kg KN046 showed promising efficacy and favorable safety profile in advanced squamous and non-squamous NSCLC patients after failure of or intolerance to previous platinum-based chemotherapy. This study provided more basis for further development of KN046 in NSCL.
About KN046
KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by Jiangsu Alphamab. Its innovative designs include: a novel mechanism - CTLA-4 fused with PD-L1 single domain antibody; engineered to target the tumor microenvironment with high PD-L1 expression, and Treg (suppress tumor immunity) clearing function.
There are about 20 clinical trials of KN046 in different stages covering more than 10 types of tumors including NSCLC, pancreatic cancer, thymic cancer, HCC, ESCC and TNBC in Australia, the US and China. The results of these clinical trials have shown an advantage in survival for patients. Alphamab Oncology has received FDA clearance to enter phase II trial of KN046 based on the clinical results in China and Australia. Moreover, KN046 has obtained the U.S. FDA's orphan drug designation for thymic epithelial tumor in September 2020. Several pivotal clinical trials are currently being conducted, among which the interim analysis of the phase III clinical study of KN046 combined with chemotherapy as the first-line treatment of NSCLC successfully met the prespecified PFS endpoint.
About Alphamab Oncology
Alphamab Oncology is a leading biopharmaceutical company dedicated to the discovery, development manufacturing and commercialization of world-class innovative biotherapeutics for cancer treatment. On December 12, 2019, Alphamab Oncology was listed on the Main Board of Hong Kong Stock Exchange, with the stock code:9966.
We have converged a professional R&D team led by top scientists, and have a complete industrial chain from early research and development of innovative drugs, process development, commercial production to clinical research.
With multiple in-house proprietary platforms of bispecifics, protein engineering and antibody screening, Alphamab Oncology has established a globally competitive and differentiated pipeline which consists of tumor monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates. Among them, 2 varieties were selected into the national special project of " New Drug Development", and 3 varieties were granted 4 orphan drug qualifications by FDA. The world's first subcutaneous PD-L1 inhibitor injection (Envafolimab) has been obtained the market approval by the Chinese National Medical Products Administration. More than 30 clinical studies have been carried out in 6 varieties in China, the United States and Australia, among which 8 studies of 3 varieties have entered the critical clinical stage in China and the United States.
To make cancer manageable and curable，Alphamab Oncology has always been guided by clinical value and patient needs, and focuses on the development of innovative, safe and affordable anti-tumor drugs to benefit patients in China and around the world.
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