Suzhou, December 7, 2023 - Alphamab Oncology (stock code: 9966.HK) announced that a two-and-a-half-year follow-up update of the Phase II clinical study of KN026 combined with docetaxel chemotherapy in first-line treatment of HER2-positive recurrent/metastatic breast cancer patients (Study No. KN026-201) at the 2023 SAN Antonio Breast Cancer Conference (SABCS 2023). The e-poster is available on the company's website at www.alphamabonc.com.
Title: Two and a half years follow-up data of HER2-targeted bispecific antibody KN026 combined with docetaxel as first-line treatment for HER2-positive recurrent/metastatic breast cancer
Submission Category：Late Breaking| Breast Cancer: Metastatic - HER2+
Poster ID: P01-29-02
First author: Prof. Qingyuan Zhang, Harbin Medical University Cancer Hospital
KN026-201 is a phase II, open label, multi-center clinical study, evaluating the efficacy, safety, and tolerability of KN026 in combination with Docetaxel in first-line treatment of HER2-positive recurrent/metastatic breast cancer. The primary endpoints were objective response rate (ORR) and duration of response (DOR) as assessed by the investigators according to RECIST 1.1, and secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety outcomes. (cutoff date: Aug 18, 2022) were presented at SABCs 2022, showed promising efficacy and tolerability. The long-term efficacy and safety of the therapy after two and a half years of follow-up will be presented.
As of data cut-off date (Sep 15, 2023), A total of 57 HER2-positive female patients with recurrent or metastatic breast cancer were enrolled. Patients received KN026 30 mg/kg combined with docetaxel 75 mg/m2 Q3W until disease progression, unacceptable toxicity, or other circumstances that require drug discontinuation.
The median follow-up was 30.6 mos (95%CI: 29.11, 31.77). Among 55 evaluable subjects, the objective response rate (ORR) was 76.4% (95% CI:62.98,86.77). Median DoR follow-up time was 28.1 months (95% CI: 26.28, 29.08), and DoR was not reached (95% CI: 20.73, NE). Median progression-free survival (mPFS) was 27.7 months (95% CI:17.97, NE), and median overall survival (mOS) was not reached. The OS rates at 12m, 24m and 30m were 93.0% (95% CI: 82.37, 97.31), 84.1% (95% CI: 71.73, 91.41) and 78.5% (95% CI: 65.16, 87.17), respectively. The mPFS of subjects with or without visceral metastasis were 23.6 mos and not reached. The mPFS of subjects with or without brain metastasis were 13.7 mos and 28.1 mos, respectively. The mPFS of 48 subjects with high HER2 expression (3+) was 28.1 mos.
Among 57 subjects, The incidence of grade 3 and above adverse events (TEAE) during treatment was 63.2%(36/57), and the incidence of grade 3 and above TRAE associated with KN026 was 43.9%(25/57), including a 24.6% decrease in neutrophil count (14/57), and a 12.3% decrease in white blood cell count (7/57). , hypokalemia 7.0%(4/57), diarrhea 3.5%(2/57), and other incidence were less than 2%. The incidence of serious adverse events (SAE) associated with KN026 was 12.3%(7/57). No deaths from adverse events related to KN026 occurred in this study.
KN026 in combination with docetaxel is well tolerated and has shown promising clinical benefit as 1L treatment for HER2-positive BC. After 2.5 years follow-up, mPFS was 27.7 mos and the 24-mos OS rate was 84.1%, which is very promising. No new safety signals were observed.
Currently, a randomized, controlled, open, multicenter Phase III clinical study of KN026 combined with Docetaxel for injection (albumin-bound) HB1801 comparing trastuzumab combined with pertuzumab and docetaxel in first-line treatment of HER2-positive relapsed metastatic breast cancer is underway. It will provide better first-line treatment options for such patients.
About KN026
KN026 is an anti-HER2 bispecific antibody that can bind two non-overlapping epitopes of HER2 simultaneously, leading to a dual HER2 signal blockade. KN026 has demonstrated superior activity comparing with Trastuzumab and Pertuzumab in combination, such as Improved 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.
Alphamab already initiated multiple clinical trials for KN026 in China and the United States. KN026 showed good efficacy and safety profiles, even in heavily pretreated patients with HER2-positive breast cancer and gastric cancer. In November 2023,the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) granted a Breakthrough Therapy designation to KN026 (HER2 bispecific antibody) combined with chemotherapy for the treatment of HER2-positive gastric cancer (including gastroesophageal junction cancer). Currently, two phase III pivotal trials of KN026 are ongoing for patients with breast cancer, or gastric cancer/gastroesophageal junction cancer, etc.
In August 2021, the company entered an agreement with JMT-Bio, a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. (stock code: 1093.HK), for the development and commercialization of KN026 in Mainland China. According to the terms of the agreement, JMT-Bio will obtain the exclusive license rights of KN026 for the development and commercialization in the indications of breast cancer and gastric or gastroesophageal junction cancers (GC/GEJ) in Mainland China (excluding Hong Kong, Macau and Taiwan).
About Alphamab Oncology
Alphamab Oncology is a 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.
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.
We have created a biological macromolecule drug discovery, research and development, manufactured technology platform with independent intellectual property rights such as protein/antibody engineering, antibody screening, multi-module/multi-functional antibody modification.
With multiple in-house proprietary technology platforms, Alphamab Oncology has established a globally competitive and differentiated pipeline which consists of tumor single domain antibody/monoclonal antibodies, multi-functional antibodies, and antibody-drug conjugates. Among them, The world's first subcutaneous PD-L1 inhibitor injection (Envafolimab) has been obtained the market approval by the Chinese National Medical Products Administration, several varieties have entered the critical clinical stage in China and the United States, 2 varieties were selected into the national special project of " New Drug Development", and 3 varieties were granted 4 orphan drug qualifications by FDA.
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