SUZHOU, China, February 24, 2022 /PRNewswire/ — Alphamab Oncology Announcement (Stock Code: 9966.HK) Clinical cancer research, a journal of the American Association for Cancer Research (AACR), has published 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 co-first authors, and Professor Xichun Hu from Fudan University Shanghai Cancer Center is the corresponding author.
This is the world’s first MBC-focused proof-of-concept clinical trial with a bispecific humanized antibody targeting HER2. Preliminary results from this study were first presented at the 2020 ASCO Annual Meeting. Updated data from this Phase I clinical study in China from this publication demonstrated that KN026 was well tolerated, showed encouraging preliminary antitumor activity and achieved promising efficacy in patients with metastatic breast cancer HER2 positive (MSC) who had progressed on at least 1 prior line of anti-HER2 therapies.
This phase I study enrolled 63 patients with HER2-positive MSC who had progressed on previous anti-HER2 treatments. Patients received KN026 as 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 assess safety and tolerability, followed by dose escalation to assess preliminary efficacy in the cohort of 20 mg/kg Q2W and 30 mg/kg Q3W.
No dose-limiting toxicity was observed at the four dose levels, and the maximum tolerated dose of KN026 was not reached. The most common treatment-related adverse events (AEs) were pyrexia (23.8%), diarrhea (22.2%), AST increased (22.2%), and blood pressure increased. ALT (22.2%). Only 4 patients reported grade 3 TEAEs. No grade 4 or 5 TRAEs were reported.
The results of the 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 RP2D levels cohort (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).
KN026 is an anti-HER2 bispecific antibody developed by Alphamab Oncology using proprietary Fc-based heterodimeric bispecific platform technology called Charge Repulsion Induced Bispecific (CRIB). KN026 can simultaneously bind two non-overlapping epitopes of HER2, resulting in dual blockade of HER2 signaling. KN026 demonstrated potentially equivalent efficacy compared to trastuzumab and pertuzumab in combination, and was superior to either agent alone, such as increased binding affinity, as well as better tumor inhibition in cell lines HER2-positive tumors. Moreover, KN026 also showed inhibitory effect on tumor cells with medium or low HER2 expression or trastuzumab resistant cell lines.
KN026 has received IND approval from the National Medical Products Administration (NMPA) of China and the United States Food and Drug Administration (FDA) in 2018. Currently, it is undergoing multiple Phase I/II clinical trials in China and phase I clinical trial in United States. Phase I clinical trial results show that KN026 exhibits good safety, tolerability and potentially superior anti-tumor activity in patients with HER2-positive breast cancer who have progressed after multiple lines of anti-inflammatory therapy. HER2.
About Alphamab Oncology
Alphamab Oncology is focused on innovation, including the discovery, development, production and commercialization of anti-tumor drugs. At December 12, 2019the company was listed on the Hong Kong Stock Exchange with stock code 9966.
Alphamab has fully integrated proprietary biological platforms in bi-specifics and protein engineering. Its highly differentiated in-house pipeline includes fifteen cancer monoclonal antibodies and bispecific antibodies and one Covid-19 bispecific antibody. Five products entered phase I-III clinical trials in China, United States, Japan and Australia and in November 2021one of these products, the unique PD-L1 antibody for subcutaneous administration, Envafolimab, has received marketing authorization from China’s National Medical Products Administration (NMPA) for the treatment of solid tumors previously processed MSI-H/dMMR advances.
The company also has state-of-the-art manufacturing capabilities designed and built to meet NMPA and EU/FDA cGMP standards and a comprehensive quality system that has passed one-person on-site inspection. qualified from the European Union. Alphamab Oncology is committed to building a global multidimensional drug development and commercialization platform, focusing on innovative multifunctional biologic drugs, and benefiting patients in China and around the world.