· Presented at this AACR meeting are the results of the JSKN003 study during the dose escalation phase (I.a).
· JSKN003 treatment of HER2-expressing advanced/metastatic solid tumors showed encouraging efficacy signals, with 100% ORR in patients with HER2-positive breast cancer. Tolerability and safety were good, DLTs did not occur, and MTD was not reached.
On April 10, 2024, Alphamab Oncology Biologics (stock code: 9966. HK) announced that it presented data from a Phase I clinical study of HER2 bispecific antibody conjugates JSKN003 for the treatment of HER2-expressing advanced solid tumors in Australia in a poster presentation at the 2024 American Association for Cancer Research Annual Meeting (AACR 2024) (Study ID: JSKN003-101).
Subject: Safety and Efficacy of JSKN003 for the Treatment of Advanced/Metastatic Solid Tumors: A First-in-Human, Dose-Escalation and Dose-Expanding, Multicenter, Open-label Phase I Study
Abstract Number: CT179
展示地点：Poster Section 48
主要研究者:Claire Beecroft
Poster Presentation: April 9, 2024, 9:00-12:30 a.m. ET
JSKN003-101 is an open-label, multicenter, dose-escalation and dose-expansion Phase I clinical study conducted in Australia to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of JSKN003 for the treatment of advanced solid tumors and to determine the recommended Phase II dose (RP2D). Presented at the AACR meeting are data from the dose-escalation phase (I.a) study in this study.
A total of 32 patients were enrolled in the study and received JSKN003 monotherapy every 3 weeks in 7 dose groups (1.0-8.4 mg/kg) during the dose escalation phase. Among them, 46.9%, 46.9% and 6.3% of patients with ECOG PS scores of 0, 1 and 2 were respectively. HER2 (IHC) 1+, 2+, and 3+ patients accounted for 28.1%, 50.0%, and 21.9%, respectively. The distribution of patients by tumor type was breast cancer (46.9%), ovarian cancer (15.6%), bladder cancer (9.4%), lung cancer (6.3%), esophageal cancer (3.1%), gastric cancer (3.1%), head and neck tumors (3.1%) and other tumor types (12.5%). 62.5% of the patients had received 3 or more lines of systemic therapy in the past.
Efficacy: As of the data cut-off date of March 15, 2024, the objective response rate (ORR) and disease control rate (DCR) were 56.3% (95% CI: 37.7%, 73.6%) and 90.6% (95% CI: 75.0%, 98.0%) for 32 patients, and 66.7% (6/9), 37.5% (6/16), and 85.7% (6/7) for patients with IHC 1+, 2+, and 3+, respectively. The ORR of HER2-positive breast cancer patients was 100% (5/5), and that of HER2-low breast cancer patients was 50% (5/10).
Safety: Treatment-related adverse events (TRAEs) occurred in 27 patients (84.4%), 4 patients (12.5%) developed grade 3 TRAEs, and 1 patient (3.1%) developed grade 2 interstitial pneumonia (7.3 mg/kg group). Common TRAEs of all grades with an incidence of more than 10% were: diarrhea (62.5%), nausea (53.1%), fatigue (21.9%), vomiting (21.9%), anorexia (18.8%), abdominal pain (12.5%), drowsiness (12.5%), and alopecia (12.5%). The incidence of hematologic toxicity is extremely low. No death or discontinuation of treatment due to TRAEs. All patients have completed the dose-limiting toxicity (DLT) observation period, no DLT events have occurred, and the maximum tolerated dose (MTD) has not been reached in the study.
PK: JSKN003 exposure increases with increasing dose, with an average half-life of 6.3 mg/kg of approximately 5 days. There was a certain accumulation after multiple doses, and the average accumulation ratio was about 1.3 at JSKN003 6.3 mg/kg dose. The exposure of free toxins was significantly lower than that of JSKN003, and the Cmax of 6.3 mg/kg was 1.21 ng/ml, indicating that the JSKN003 had good stability in the circulatory system in vivo.
Conclusions: JSKN003 is well tolerated and safely preserved in patients with advanced/metastatic solid tumors who have been previously treated with multiple lines of systemic therapy, and has shown encouraging preliminary antitumor activity. The incidence of hematotoxicity and interstitial lung disease (ILD) is low (grade 2 ILD occurred in only one patient). As of the data cut-off date, all patients had completed the dose-limiting toxicity (DLT) observation period, no DLT events had occurred, and the MTD had not been reached.
About JSKN003
JSKN003 is a novel antibody-drug conjugate (ADC) targeting HER2 biepitope, which is independently developed by Alphamab Oncology using its unique glycan site-directed conjugation platform. JSKN003 bind to HER2 on the surface of tumor cells and release topoisomerase I inhibitors through HER2-mediated endocytosis, thereby exerting antitumor effects. Preclinical studies have shown that JSKN003 has better serum stability, stronger bystander killing effect and equivalent tumor killing activity than similar drugs, effectively expanding the therapeutic window. At present JSKN003 a number of clinical studies are being carried out in Australia and China, and the indication of HER2-low expression breast cancer has entered the phase III clinical stage in China.
About Alphamab Oncology
Alphamab Oncology is an innovative biopharmaceutical company dedicated to discovering, developing, manufacturing and commercializing world-class oncology therapies for patients. On December 12, 2019, the company was listed on the main board of the Hong Kong Stock Exchange (stock code: 9966.HK). HK）。
Alphamab Oncology has established a technology platform for the R&D and production of biomacromolecule drugs such as protein/antibody engineering, antibody screening, and multi-module/multi-functional antibody modification with independent intellectual property rights. It has built a product pipeline with significant differentiation and strong international competitiveness, covering innovative anti-tumor drugs such as single-domain antibodies/monoclonal antibodies, multifunctional antibodies and antibody conjugates: one of the products, KN035 (the world's first subcutaneous PD-(L)1 inhibitor, envafolimab injection, trade name: Envida ®) has been approved for marketing in China in 2021, becoming a widely accessible drug for cancer patients, 3 products are in late-stage clinical development, and KN026, a HER2 bispecific antibody, has been granted Breakthrough Therapy Designation by the NMPA in China. In addition, the company has a rich early-stage R&D pipeline, of which 2 new drug molecules have entered the clinical research stage.
"Kangda patients, Ruiji Wanjia". Alphamab Oncology has always focused on unmet clinical needs and continues to develop safe, affordable and globally competitive anti-tumor drugs to benefit patients.
Welcome to the company's website: www.alphamabonc.com
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