● As of May 8, 2021, A total of 44 patients were enrolled and received at least one infusion of KN026 and/or KN046. 36 patients received at least one imaging assessment. For HER2-positive patients, ORR was 51.9% and the median DOR was 11.2 months. The ORR was 71.4% for treatment naïve patients. 18.2% of patients encountered more than one grade ≥3 TRAE.
Suzhou, Sep 17, 2021 - Alphamab Oncology (stock code: 9966.HK) announced that data from a Phase Ib study (KN046-IST-02) of KN026 plus KN046 for gastrointestinal tumors (GI) with HER2 positive/mutation/low-expression are presented as Poster at the ESMO (European Society for Medical Oncology) congress 2021.
KN026 is a biparatopic bispecific antibody that targets the domains II (Pertuzumab binding site) and IV (Trastuzumab binding site) of HER2. KN046 is a tetravalent bispecific antibody that can simultaneously recognize PD-L1 and CTLA-4. KN046-IST-02 is a phase Ib clinical study to explore safety and efficacy of KN026 combined with KN046 (chemo-free therapy) for advanced HER2 positive GI tumors including tumors with mutation or low-expression. The preliminary results of the study (mainly including the efficacy data of HER2 positive GI cancers and safety of KN026 combined with KN046) have been presented as Poster at ESMO congress 2021 at Sep 16. The e-poster is available from company website www.qqkjdm.cn.
Title: Preliminary Efficacy and Safety Results of KN026 (a HER2-targeted Bispecific Antibody) in Combination with KN046 (an anti-PD-L1/CTLA-4 Bispecific Antibody) in Patients (pts) with HER2-positive Gastrointestinal Tumors
Poster number: 1377P
First author: Jifang Gong, Beijing Cancer Hospital
This ongoing phase Ib clinical study enrolled patients with histologically or cytologically confirmed unresectable locally advanced or metastatic GI cancer with HER2 positive/mutation/low-expression in China. Both prior treated or treatment naïve patients were enrolled. This study included a dose escalation and expansion part. Efficacy assessments were performed every 8 weeks according to RECIST 1.1. The primary endpoint was dose limiting toxicity (DLT) in the dose escalation phase, and objective response rate (ORR), duration of response (DOR) and safety in the dose expansion phase.
As of May 8,2021, 44 patients were enrolled, median age (range) was 56 (29-74) years, 39 patients were ECOG PS 1, 34 patients were HER2 positive, and 24 patients were HER2-positive GC/GEJ, 10 patients had received trastuzumab. In the study, 90.9% of patients encountered at least one treatment related adverse event (TRAE), and the common were anemia (38.6%), infusion related reaction (36.4%), AST increased (27.3%), diarrhea (27.3%), ALT increased (25.0%), rash (20.5%), etc. 18.2% of patients encountered at least one grade ≥3 TRAE and the most common was anemia (4.5%). For 36 evaluable patients the ORR was 38.9% with median DOR 11.2 months. In 27 HER2-positive patients, the ORR was 51.9% with median DOR 11.2 months; Among those 27 patients 21 were GC/GEJ, the ORR was 71.4% for treatment naïve patients (n=7), 42.9% for 14 patients who had been exposed to systemic therapy and 40.0% for 10 patients who had received trastuzumab.
Professor Lin Shen from Beijing Cancer Hospital, the principal investigator of the clinical trial, commented, “Chemotherapy is still the main treatment of advanced GI, however, it has major toxic side effects and sooner or later leads to drug resistance. We are pleased to see that KN026 combined KN046, as chemo-free therapy, showed promising efficacy for HER2-positive GI, especially for 1st line HER2-positive GC/GEJ with a high ORR of 71.4%. The standard treatment for 1st line HER2-positive GC/GEJ is trastuzumab combined with chemotherapy, and the ORR is only 40% to 50%. We look forward to exploring potential value of the combined therapy for HER2 GI patients in follow-up clinical studies and bringing new hope for patients in need."
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.
KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by Jiangsu Alphamab. Its innovative designs include: a different 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, thymic cancer, pancreatic cancer, HCC , ESCC and TNBC in Australia and China. The results of these clinical trials have shown an advantage in survival for patients. Alphamab 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. Four pivotal clinical trials are currently being conducted.
About Alphamab Oncology
Alphamab Oncology is focusing on innovation, 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 fully integrated proprietary biologics platforms in bi-specifics and protein engineering. Its highly differentiated in-house pipeline includes fifteen tumor monoclonal antibodies and bispecific antibodies and a Covid-19 bispecific antibody. Four products have advanced into phase I-III clinical trials or pre-marketing stage in China, the United States, Japan and Australia. The BLA for Envafolimab (KN035) has been accepted and granted Priority Review by the National Medical Products Administration (NMPA).
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.
Visit http://www.qqkjdm.cn for more information.
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