Suzhou, China, February 6, 2024 - Alphamab Oncology (stock code: 9966.HK) announced that the phase Ⅱclinical research results of anti- PD-L1/CTLA-4 bispecific antibody KN046 in combination with nab-paclitaxel as first-line treatment in advanced triple-negative breast cancer (TNBC) were published online in the renowned journal Nature Communications (IF: 16.6, JCR Q1). Professor Binghe Xu from Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College is the corresponding author of this paper.
Corresponding Author: Binghe Xu,
First author: Qiao Li
KN046-203 is a phase II, open label, multi-center, multi-cohorts clinical study, evaluating the efficacy, safety, and tolerability of KN046 in combination with nab-paclitaxel in patients with TNBC as first-line treatment. A total of 27 female patients who were systemic treatment naïve for locally advanced inoperable or metastatic TNBC were enrolled.
As of August 21, 2022, based on the Independent Review Committee (IRC) evaluation, the objective response rate (ORR) from 25 efficacy evaluable TNBC patients was 44.0% (95% CI: 24.4~65.1%), the disease control rate (DCR) was 96.0% (95% CI: 79.7~99.9%), the clinical benefit rate (CBR) was 52.0% (95% CI: 31.1~72.2%) and the median DOR was not mature. The progression-free survival (PFS) and overall survival (OS) was analyzed on intention-to treat (ITT) population. The median PFS was 7.33 months (95%CI: 3.68~11.07 months). Among the patients with PD-L1 expression ≥1%, the median PFS was 8.61 months (95%CI, 1.61 - NE months). The median OS result was 30.92 months (95% CI, 14.75 - NE months), and the 2-year OS rate was 60.1% (95%CI, 37.2~76.9%). Both PD-L1 negative and positive patients could derive OS benefit from the therapy.
Among the 27 evaluable patients, Grade 3-4 treatment-related adverse events (TRAEs) occurred in 18 patients (66.7%). Treatment-related serious adverse events (TRSAEs) occurred in 6 patients (22.2%). Immune-related adverse events (irAEs) occurred in 13 patients (48.1%). Most irAEs were Grade 1 or 2. Grade ≥3 irAEs were reported in 3 patients, 2 patients with Grade 3 immune-mediated liver disease, and 1 patient with Grade 3 rash.
Conclusion: KN046 combined with nab-paclitaxel in the first-line treatment of TNBC showed encouraging PFS and OS. Patients received combination therapy were well tolerated and the safety profile was manageable.
About KN046
KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by 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 committed to the discovery, development, manufacturing, and commercialization of cutting-edge biotherapeutics for the treatment of cancer. On December 12, 2019, the company was successfully listed on the Main Board of the Hong Kong Stock Exchange, trading under the stock code 9966.
Our integrated platform seamlessly combines research, development, and manufacturing capabilities for biologics. We take pride in our extensive intellectual property portfolio, encompassing protein/antibody engineering, antibody screening, and multi-module/multi-functional antibody modification.
Distinguished by a globally competitive pipeline, Alphamab Oncology specializes in antibody-drug conjugation, single domain antibody/monoclonal antibodies, and multi-functional antibodies. Notably, Envafolimab, the world's first subcutaneously injectable PD-L1 inhibitor, received approval from Chinese authorities in 2021, offering widespread accessibility to cancer patients. Three additional products are currently in the advanced stages of clinical development, with KN026 having earned Breakthrough Designation from the China National Medical Products Administration. Furthermore, we have cultivated a series of early-stage assets, including two in Phase I development.
Our overarching mission is to enhance the manageability and curability of cancer by addressing unmet medical needs in oncology. Alphamab Oncology is dedicated to the development of safe and affordable drugs, leveraging a global competitive edge.
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