Alphamab Oncology is making significant strides in its clinical development programs with JSKN003 and JSKN033, targeting a range of cancers with high unmet needs. These advancements include the initiation of Phase III trials for JSKN003 in ovarian and breast cancers, as well as the approval to begin Phase I/II trials for JSKN033 in advanced metastatic malignant tumors.
Phase III Trial of JSKN003 in Platinum-Resistant Ovarian Cancer
Alphamab Oncology announced that the first patient has been dosed in the Phase III clinical study (Study ID: JSKN003-306) of anti-HER2 biparatopic antibody-drug conjugate (ADC) JSKN003. This trial is designed to evaluate the efficacy of JSKN003 compared to investigator-selected chemotherapy in patients with platinum-resistant recurrent epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, regardless of HER2 expression levels.
Ovarian cancer is a significant concern in China, ranking as the third most common gynecologic malignancy with a high mortality rate. Approximately 70% of ovarian cancer cases recur after treatment, progressing to platinum-resistant ovarian cancer (PROC), which has limited effective treatment options. The JSKN003-306 trial is a randomized, open-label, parallel-controlled, multi-center study that aims to address this critical need.
JSKN003, developed using Alphamab's Glycan-specific conjugation platform, has demonstrated better serum stability and a stronger bystander effect compared to other ADCs, potentially expanding the therapeutic window. Data from Phase I clinical studies presented at the 2024 ESMO Congress indicated promising efficacy signals with JSKN003 monotherapy in patients with advanced PROC, irrespective of HER2 expression or prior treatments.
IND Approval for JSKN033 Phase I/II Trial
The China National Medical Products Administration’s (NMPA) Center for Drug Evaluation (CDE) has approved Alphamab Oncology’s investigational new drug application (IND) for the multicenter Phase I/II JSKN033-102 trial of JSKN033. JSKN033 is a high-concentration subcutaneous co-formulation that includes an anti-human epidermal growth factor receptor 2 (HER2) bispecific antibody-drug conjugate (ADC) and a PD-L1 immune checkpoint inhibitor.
By combining immunotherapy with ADC, JSKN033 has the potential to significantly improve efficacy. The approved open-label trial is aimed at assessing the safety, tolerability, anti-tumour activity, and pharmacokinetic/pharmacodynamic properties of the therapy in individuals with advanced metastatic malignant tumours. It will also determine the maximum tolerated dose (MTD) and/or the recommended Phase II dose (RP2D).
The initial Phase I/II JSKN033-101 trial conducted in Australia has shown a ‘favourable’ safety profile and ‘positive’ anti-cancer activity in subjects heavily treated. JSKN033 is said to be the first to enter first-in-human clinical trials. Building on the solubility and stability of a subcutaneously injectable humanised PD-L1 inhibitor, Envaforlimab, JSKN033 combines immunotherapy (KN035) with ADC (JSKN003).
Phase III Trial of JSKN003 in HER2-Positive Breast Cancer
Alphamab Oncology and CSPC Pharmaceutical Group Co., Ltd. jointly announced that anti-HER2 biparatopic antibody-drug conjugate (ADC) JSKN003 has received approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) to initiate a Phase III clinical study (Study ID: JSKN003-301). The study aims to compare the efficacy and safety of JSKN003 versus trastuzumab emtansine (T-DM1) for the treatment of HER2-positive advanced breast cancer.
HER2-positive breast cancer accounts for 20% to 25% of all breast cancer cases in China and is known for its aggressive nature, recurrence, and metastasis. While targeted therapies have improved outcomes, there remains a significant unmet clinical need for recurrent and metastatic cases.
JSKN003-301 is a randomized, controlled, open-label, multicenter, Phase III clinical study aimed at evaluating the efficacy and safety of JSKN003 compared to emtansine (T-DM1) in the treatment of patients with HER2-positive, unresectable locally advanced or metastatic breast cancer who have previously received trastuzumab or taxane-based therapies. The primary endpoint of the study is progression-free survival (PFS) as assessed by the Blinded Independent Review Committee (BIRC).
JSKN003, developed with Alphamab's Glycan-specific conjugation platform, binds to HER2 on tumor cells and releases topoisomerase I inhibitors (TOPIi), exerting anti-tumor effects. It has shown better serum stability and a stronger bystander effect compared to other ADCs, potentially expanding the therapeutic window.
These clinical advancements underscore Alphamab Oncology's commitment to developing innovative biotherapeutics for cancer treatment, addressing unmet clinical needs, and improving patient outcomes.
