Suzhou, China, February 24 2022 - Alphamab Oncology (stock code: 9966.HK) announced Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR), published the data from a phase I clinical study of the company's proprietary HER2 bispecific antibody KN026 for the treatment of HER2-positive metastatic breast cancer (“First-in-human HER2-targeted Bispecific Antibody KN026 for the Treatment of Patients with HER2-positive Metastatic Breast Cancer: Results from a Phase I Study”，https://aacrjournals.org/clincancerres/article/28/4/618/678114/First-in-human-HER2-targeted-Bispecific-Antibody) . Professor Jian Zhang and Dr. Dongmei Ji from Fudan University Shanghai Cancer Center are the co–first authors, and Professor Xichun Hu from Fudan University Shanghai Cancer Center is the corresponding author.
This is the world’s first proof-of-concept clinical trial focusing on MBC with a bispecific humanized antibody targeting HER2. The preliminary results of this study were first presented at the 2020 ASCO annual meeting. The updated data of this China Phase I clinical study from this publication demonstrated that KN026 was well tolerated, showed encouraging preliminary antitumor activity and achieved promising efficacy in patients with HER2-positive metastatic breast cancer (MBC) who had progressed on at least 1 prior line of anti-HER2 therapies.
This phase I study enrolled 63 patients with HER2-positive MBC who had progressed on prior anti-HER2 therapies. Patients received KN026 monotherapy at 5 mg/kg QW, 10 mg/kg QW, 20 mg/kg Q2W, or 30 mg/kg Q3W. Dose escalation was guided by a “3+3” dose escalation rule to evaluate the safety and tolerability, followed by dose expansion to evaluate preliminary efficacy in the cohort of 20 mg/kg Q2W and 30 mg/kg Q3W.
No dose-limiting toxicity was observed in all four dose levels, and the maximal tolerated dose of KN026 was not reached. The most common treatment-related adverse events (AE) were pyrexia (23.8%), diarrhea (22.2%), AST increased (22.2%), and ALT increased (22.2%). Only 4 patients reported Grade 3 TRAEs. No TRAEs of Grade 4 or 5 were reported.
Results from exposure-response analysis supported the selection of the recommended phase II doses (RP2D) at 20 mg/kg Q2W or 30 mg/kg Q3W. Of 57 patients in the cohort of RP2D Levels (20 mg/kg Q2W and 30 mg/kg Q3W), the median progression-free survival (mPFS) was 6.8 months (95% CI: 4.2-8.3).
About KN026
KN026 is an anti-HER2 bispecific antibody developed by Alphamab Oncology using the proprietary Fc-based heterodimer bispecific platform technology called CRIB (Charge Repulsion Induced Bispecific). KN026 can bind two non-overlapping epitopes of HER2 simultaneously, leading to a dual HER2 signal blockade. KN026 has demonstrated potentially equivalent efficacy compared with Trastuzumab and Pertuzumab in combination, and was superior to either single agent, such as increased binding affinity, as well as better tumor inhibition in HER2-positive tumor cell lines. Additionally, KN026 has also shown inhibitory effect on tumor cells with medium or low HER2 expression or Trastuzumab-resistant cell lines.
KN026 received IND approval from the National Medical Products Administration (NMPA) of China and U.S. Food and Drug Administration (FDA) in 2018. Currently, it is in multiple phase I/II clinical trials in China and phase I clinical trial in the United States. The results of Phase I clinical trials show KN026 has good safety, tolerance and potentially superior anti-tumor activity in HER2-positive breast cancer patients who progressed after multiple lines of anti-HER2 treatment.
About Alphamab Oncology
Alphamab Oncology is focusing on innovation, including discovery, development, production and commercialization of anti-tumor drugs. On December 12, 2019, the Company was listed in the mainboard of Hong Kong Stock Exchange with stock code 9966.
Alphamab has a fully integrated proprietary biologics platforms in bi-specifics and protein engineering. Its highly differentiated in-house pipeline includes fifteen anticancer monoclonal antibodies and bispecific antibodies and a Covid-19 bispecific antibody. Five products have advanced into phase I-III clinical trials in China, the United States, Japan and Australia and in November 2021, one of these products, the unique PD-L1 antibody for subcutaneous administration, Envafolimab, received marketing authorization from the Chinese National Medical Products Administration (NMPA) for the treatment of previously treated MSI-H/dMMR advanced solid tumors.
The Company also has state-of-the-art manufacturing capabilities designed and built to meet NMPA and EU/FDA’s cGMP standards and a complete quality system which has passed the on-site inspection of a European Union qualified person. Alphamab Oncology is committed to building a global leading, multi-dimensional drug development and commercialization platform, focusing on multifunctional biological innovative drugs, and to benefit patients in China and around the world.
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