Alphamab Oncology updated clinical research data for KN026 in Combination with KN046 in HER2-Positive Solid Tumors at the ASCO 2023 annual meeting

• As of November 10, 2022, 26 patients with HER2-positive unresectable or metastatic solid tumors (other than breast cancer and gastric/gastroesophageal junction cancer) were enrolled, 92.3% of whom had received ≥2L prior systemic therapy. The objective response rate (ORR) was 53.8% with 6.8 months median duration of response (mDOR), 5.6 months median progression survival (mPFS) and 80.4% 12-month overall survival (OS) rate.
• For 15 CRC patients, the ORR was 53.3% with mDOR 11.7 months, mPFS 12.2 months and 80.0% 12-month OS rate.

SUZHOU, China, June 6, 2023 /PRNewswire/ -- Alphamab Oncology (stock code: 9966.HK) announced that updated data from the phase II clinical study of the chemo-free regimen of KN026 in combination with KN046 (KN026-203) were presented at the 2023 American Society of Clinical Oncology (2023 ASCO) Annual Meeting. The e-poster can be accessed on the company's website at www.alphamabonc.com.

KN026-203 is a single-arm, open-label, multi-cohort, multi-center phase II clinical study to evaluate the efficacy and safety of KN026 in combination with KN046 in the treatment of HER2-positive solid tumors. 102 patients were recruited including 3 cohorts: HER2-positive GC/GEJ, breast cancer as well as other solid tumors that have received ≥1L systemic treatment. The preliminary clinical results from other solid tumor cohort were first presented in April 2022 at the Annual Meeting of the American Association for Cancer Research (AACR). The data released at ASCO includes a larger population of patients for efficacy analysis and a longer follow-up period, compared with results of AACR poster.

As of November 10, 2022, 26 patients with HER2-positive unresectable or metastatic solid tumors, including 15 CRC patients, 5 NSCLC patients, 4 biliary tract cancer patients, 1 renal pelvis cancer patient and 1 pancreatic cancer patient, were enrolled, 92.3% of whom had received ≥2L prior systemic therapy. Patients received KN046 (iv.5mg/kg Q3W) combined with KN026 (iv.30mg/kg Q3W, with a loading dose on D8) treatment until progression, unacceptable toxicity or patient withdrawal. The primary endpoint was ORR and DOR assessed by the investigator Q6W according to RECIST 1.1.

All 26 patients were included in the assessment of efficacy and safety. The objective response rate (ORR) was 53.8% (95% CI: 33.4, 73.4) with median duration of response (mDOR) 6.8 months (95% CI: 2.9, 15.3). The median progression free survival (mPFS) was 5.6 months (95% CI: 2.9, 16.5) and 12-month overall survival (OS) rate was 80.4% (95% CI: 59.1, 91.4). For 15 CRC pts, the ORR was 53.3% (95% CI: 26.6, 78.7) with mDOR 11.7 months (95% CI: 3.2, NE). The mPFS was 12.2 months (95% CI: 2.7, NE). 12-month OS rate was 80.0% (95% CI: 50.0, 93.1).

As for safety, 25 of 26 patients (96.2%) had experienced treatment-related adverse event (TRAEs) of any grade, and total 9 of 26 patients (34.8%) had experienced ≥grade 3 TRAEs. The most common (≥20%) TRAEs were infusion related reaction (10,38.5%), AST increased (9,34.6%), conjugated bilirubin increased (7,26.9%), ALT increased (7,26.9%), anemia (7,26.9%), blood bilirubin increased (7,26.9%) and rash (7,26.9%). No treatment-related deaths were observed.

About KN026

KN026 is an anti-HER2 bispecific antibody invented 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 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 KN046

KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by Jiangsu 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 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.

We have converged a professional R&D team led by top scientists, and have a complete industrial chain from early research and development of innovative drugs, process development, commercial production to clinical research.

With multiple in-house proprietary platforms of bispecifics, protein engineering and antibody screening, Alphamab Oncology has established a globally competitive and differentiated pipeline which consists of tumor monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates. Among them, 2 varieties were selected into the national special project of "New Drug Development", and 3 varieties were granted 4 orphan drug qualifications by FDA. The world's first subcutaneous PD-L1 inhibitor injection (Envafolimab) has been obtained the market approval by the Chinese National Medical Products Administration. More than 30 clinical studies have been carried out in 6 varieties in China, the United States and Australia, among which 8 studies of 3 varieties have entered the critical clinical stage in China and the United States.

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.

SOURCE Alphamab Oncology