The dose-escalation results of JSKN003 was reported at this AACR conference. JSKN003 exhibited a favorable tolerability, safety profile and encouraging preliminary antitumor activity in patients with HER2-expressing advanced/metastatic solid tumors. The ORR in patients with HER2+ BC was 100%. No DLT was observed, MTD has not been reached yet.
SUZHOU, China, April 10, 2024 /PRNewswire/ — Alphamab Oncology (stock code: 9966.HK) announced the data from phase I clinical study conducted in Australia (JSKN003-101) of anti-HER2 bispecific antibody-drug conjugate (ADC) JSKN003 for the treatment of HER2-expressing advanced solid tumors, were presented as a poster at the American Association for Cancer Research Annual Meeting 2024 (AACR 2024).
Title: Safety and efficacy of JSKN003 in patients with advanced/metastatic solid tumors: A first-in-human, dose-escalation and expansion, multicenter, open-label, phase I study
Abstract ID: CT179
Location: Poster Section 48
Leading PI: Claire Beecroft
Poster release time: Apr 9, 2024, 9:00 AM- 12:30 PM EDT
JSKN003-101 is an open-label, multi-center, dose-escalating (phase Ia) and dose-expansion (phase Ib) clinical study conducted in Australia. The primary endpoint is to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of JSKN003 in the treatment of advanced solid tumors, as well as to determine the recommended phase II dose (RP2D). The dose-escalation results of this study was reported at this AACR conference.
32 patients were enrolled and received JSKN003 during the dose-escalation part across 7 dose levels (1.0 – 8.4 mg/kg, Q3W). The proportion of patients with ECOG PS score 0, 1 and 2 was 46.9%, 46.9% and 6.3%, respectively. The proportion of patients with HER2 (IHC) 1+, 2+ and 3+ was 28.1%, 50.0% and 21.9%, respectively. The distribution of cancer types included breast cancer(46.9%), ovarian cancer(15.6%), bladder cancer(9.4%), lung cancer(6.3%), esophageal cancer(3.1%), stomach cancer(3.1%), head and neck cancer(3.1%) and other tumors(12.5%). 62.5% of patients had ≥3 prior lines of systemic treatment.
Efficacy: As of the cut-off date March 15, 2024, the objective response rate (ORR) and disease control rate (DCR) was 56.3% (95%CI: 37.7%, 73.6%) and 90.6% (95%CI: 75.0%, 98.0%), respectively. The ORR in patients with IHC 1+, 2+ and 3+ was 66.7% (6/9), 37.5% (6/16), and 85.7% (6/7), respectively. As for the efficacy of the HER2+ BC and HER2-low BC, the ORR was 100% (5/5) and 50.0% (5/10), respectively.
Safety: Treatment-related adverse events (TRAEs) occurred in 27 patients (84.4%) and only 4 patients (12.5%) experienced grade 3 TRAE. One patient experiencedgrade 2 interstitial lung disease (ILD) (1/32, occurred in 7.3 mg/kg). The most commonly reported TRAEs (≥10%) were diarrhea(62.5%), nausea(53.1%), fatigue(21.9%), vomiting(21.9%), decreased appetite(18.8%), abdominal pain(12.5%), lethargy(12.5%), and alopecia(12.5%). The occurrence of hematologic toxicity was very low. No TRAE led to death or treatment discontinuation. All the subjects had finished dose limited toxicity (DLT) observation, and no DLT events were identified yet. Maximum tolerated dose (MTD) has not been reached in 8.4 mg/kg.
PK: Exposures (Cmax and AUC) of JSKN003 increased with dose escalation and the mean half-life of JSKN003 is approximately 5 days for 6.3 mg/kg. The mean accumulation ratio following 6.3 mg/kg multiple doses was approximately 1.3-fold for JSKN003. The exposure of released payload was significantly lower than JSKN003, with Cmax of 1.21ng/ml for 6.3 mg/kg, demonstrating the stability of JSKN003 in circulation.
Conclusion: JSKN003 demonstrated encouraging preliminary antitumor activity in heavily pretreated patients with advanced/metastatic solid tumors, and exhibited a favorable tolerability and safety profile with low occurrence of hemotoxicity and ILD (only one patient experienced grade 2 ILD). As of the cut-off date, all the subjects had finished DLT observation period, and no DLT was observed, MTD has not been reached yet.
About JSKN003
JSKN003 is an anti-HER2 bispecific antibody-drug conjugate (bis-ADC), which is developed inhouse with proprietary Glycan-specific conjugation platform. JSKN003 targets HER2 and triggers internalization and release the cytotoxic drug. Compared with its counterparts, JSKN003 demonstrated better serum stability, stronger bystander effect and comparable tumor killing activity, which effectively expands the therapeutic window. Multiple clinical studies are ongoing in Australia and China. Recently a phase III trial in HER2 low expression breast cancer has been initiated.
About Alphamab Oncology
Alphamab Oncology is a leading biopharmaceutical company committed to the discovery, development, manufacturing, and commercialization of cutting-edge biotherapeutics for the treatment of cancer. On December 12, 2019, the company was successfully listed on the Main Board of the Hong Kong Stock Exchange, trading under the stock code 9966.
Our integrated platform seamlessly combines research, development, and manufacturing capabilities for biologics. We take pride in our extensive intellectual property portfolio, encompassing protein/antibody engineering, antibody screening, and multi-module/multi-functional antibody modification.
Distinguished by a globally competitive pipeline, Alphamab Oncology specializes in antibody-drug conjugation, single domain antibody/monoclonal antibodies, and multi-functional antibodies. Notably, Envafolimab, the world’s first subcutaneously injectable PD-L1 inhibitor, received approval from Chinese authorities in 2021, offering widespread accessibility to cancer patients. Three additional products are currently in the advanced stages of clinical development, with KN026 having earned Breakthrough Designation from the China National Medical Products Administration. Furthermore, we have cultivated a series of early-stage assets, including two in Phase I development.
Our overarching mission is to enhance the manageability and curability of cancer by addressing unmet medical needs in oncology. Alphamab Oncology is dedicated to the development of safe and affordable drugs, leveraging a global competitive edge.
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