Alphamab Oncology updated data from two studies of KN026 in combination with docetaxel for HER2-positive breast cancer at ESMO

• KN026 combined with docetaxel has significant efficacy in the first-line treatment of HER2-positive recurrent or metastatic breast cancer, with mPFS of 26.9 months and 24-month OS rate of 84.2%.
• KN026 combined with docetaxel has significant efficacy and good tolerability in the neoadjuvant treatment of HER2-positive early or locally advanced breast cancer, with tpCR rate of 56.7%, bpCR rate of 60%, ORR of 90.0%. and confirmed ORR of 86.7%
• A Phase III clinical study of KN026 combined with injectable docetaxel (albumin-bound) for the first-line treatment of HER2-positive recurrent and metastatic breast cancer is ongoing.

SUZHOU, China, Oct. 24, 2023 /PRNewswire/ -- Alphamab Oncology (stock code: 9966.HK) announced the results of two studies of HER2 bispecific antibody KN026 at the European Society of Medical Oncology (ESMO) Annual Meeting, held October 20-24 in Madrid, Spain.

Title: Two-year follow-up data on the efficacy and safety of KN026, a HER2-targeted bispecific antibody combined with docetaxel as first-line treatment for HER2-positive recurrent /metastatic breast cancer
Poster ID: 418P
Corresponding Author: Prof. Qingyuan Zhang, Harbin Medical University Cancer Hospital
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 as first-line treatment for HER2-positive recurrent/metastatic breast cancer. Primary results from this study (Poster ID: PD18-08, data as of Aug 18, 2022) were presented at SABCS 2022, showed promising efficacy and tolerability. The 2-year follow-up results are updated at the 2023 ESMO annual meeting.

As of the date of data cut-off, August 4, 2023, 57 subjects were enrolled, the median age was 52 years (min:30, max:67), 100% were female, and 91.2 % (52/57) were stage IV. The most common sites of metastasis were lymph nodes, bone, lung, and liver.

The confirmed ORR within 55 evaluable subjects was 76.4% (42/55) and DCR was 100% (95% CI 93.51, 100). mDoR follow-up time was 26.3 months (95% CI 23.92, 28.91) and DoR was 26.8m (95% CI 20.73, NE). The median study follow-up was 29.7m (95%CI: 28.32, 30.59). The mPFS was 26.9 months (95% CI:17.97, NE) (Figure 5）and the mOS was not reached. The OS rates at 12m, 24m and 30m were 93.0% (95% CI: 82.37, 97.31), 84.2% (95% CI: 71.85, 91.45) and 77.9% (95% CI: 64.17, 86.89). Subjects with no visceral metastases, no brain metastases, or IHC3+ had longer PFS.

The incidence of ≥Grade 3 TEAE was 61.4% (35/57). There were no deaths due to KN026 drug-related AEs in this study. The incidence of KN026-related Grade≥3 TRAE was 40.4% (23/57), including neutrophil count decreased 24.6% (14/57), white blood cell count decreased 12.3% (7/57) and others less than 10%. The incidence of serious adverse events related to KN026 was 10.5% (6/57), including febrile neutropenia 1.8% (1/57), diarrhea 1.8% (1/57), and others.

KN026 in combination with docetaxel is well tolerated and has shown promising clinical benefit as 1L treatment for HER2-positive BC. After 2 years follow-up, mPFS was 26.9m and the 24-month OS rate was 84.2%, which is very promising. Robustness of efficacy and safety results will be further confirmed in an ongoing randomized phase 3 clinical trial with PTH as control group.

Title: KN026 in combination with docetaxel as neoadjuvant treatment for HER2+ early or locally advanced breast cancer (BC): A single arm, multicenter, phase 2 study
Poster ID: 247P
Corresponding Author：Prof. Jiong Wu, Fudan University Shanghai Cancer Center
First author: Dr. Linxiaoxi Ma, Fudan University Shanghai Cancer Center

KN026-208 (NCT04881929) is a phase II, open label, multi-center clinical study, evaluating the efficacy, safety, and tolerability of KN026 in combination with docetaxel as neoadjuvant treatment for HER2-positive early or locally advanced breast cancer. patients were enrolled to receive 4 cycles of KN026 (30mg/kg, ivgtt d1, q3w) and docetaxel (75 mg/m2 ivgtt d1, q3w) neoadjuvant treatment. The primary endpoint was total pCR rate (tpCR rate). Secondary endpoints were pCR in the breast (bpCR rate), ORR (objective response rate), safety，PK (pharmacokinetics) and immunogenicity.

Preliminary efficacy and safety results (cut-off date: Sep 10th,2022)were presented at SABCS 2022 (Poster ID: OTC-16-04), showed promising efficacy and safety. The final results are updated at the 2023 ESMO annual meeting.

From August 9th, 2021, to July 29th, 2022, a total of 30 patients (pts) were enrolled from 5 sites. As of Nov 21st, 2022, the study completed the primary outcome. 28 pts completed the surgery followed by pathological evaluation, and 2 pts discontinued from the study earlier due to AEs. In FAS, tpCR rate was 56.7% (17/30, 95% CI: 37.43%-74.54%), posterior probability for tpCR>40% was 96.7%; bpCR rate was 60% (18/30, 95% CI:40.60%-77.34%); ORR was 90.0% (27/30, 95% CI: 73.47%-97.89%); confirmed ORR was 86.7% (26/30, 95% CI:69.28%-96.24%).

The incidence of CTCAE Grade ≥3 TEAEs was 53.3% (16/30). The most common (≥5%) Grade ≥3 TEAEs were neutrophil count decreased (50.0%, 15/30), white blood cell count decreased (40.0%, 12/30), and lymphocyte count decreased (10.0%, 3/30). The incidence of SAE and CTCAE Grade≥3 SAE were both 6.7% (2/30). KN026-related SAE occurred in only one patient. No patient had left ventricular ejection fraction (LVEF) declines 10% points or more from baseline accompanied with LVEF<50%; and no patient had LVEF declines 15 % points or more from baseline.

KN026 combined with docetaxel as neoadjuvant treatment has shown promising clinical benefit for patients with HER2-positive early or locally advanced breast cancer with an acceptable and manageable safety profile.

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 potentially superior efficacy to Trastuzumab and Pertuzumab in combination, 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.

Alphamba 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. Currently, several phase III pivotal studies 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.

SOURCE Alphamab Oncology