공고 • Sep 16
Alphamab Oncology Presented the Latest Clinical Data from Two Studies on Anti-Her2 Bispecific Adc Jskn003 At the Esmo Congress 2024
Alphamab Oncology announced that the latest clinical data from two studies on anti-HER2 bispecific antibody-drug conjugate JSKN003 were presented at the 2024 European Society for Medical Oncology Congress (ESMO Congress 2024) from September 13 to 17, 2024, in Barcelona, Spain. Both were pooled analysis of two phase I clinical studies of JSKN003 conducted in Australia and China on platinum-resistant ovarian cancer and advanced HER2-positive (IHC 3+) solid tumors. Ovarian cancer is one of the three major malignant tumors of the female reproductive system. It is often diagnosed at an advanced stage, with a high recurrence rate, posing a serious threat to women's health. The standard treatment regimens recommended by authoritative guidelines both domestically and internationally include surgery combined with platinum-based chemotherapy and targeted therapy maintenance. However, about 70% of ovarian cancer cases recur after treatment and progress to platinum-resistant, with approximately 20% of patients exhibiting primary platinum resistance. The 2024 NCCN guideline recommend non-platinum cytotoxic drugs and targeted monotherapy as the preferred treatment option for patients with platinum-resistant ovarian cancer. Previous studies have shown that the objective response rate of platinum-resistant ovarian cancer treated with non-platinum chemotherapy alone is only 4% to 13%, highlighting an urgent need for new treatment options. Methods: JSKN003-101 (NCT05494918) is a phase I dose-escalation and dose-expansion study in Australian patients with advanced/metastatic solid tumors. JSKN003-102 (NCT05744427) is a phase I (dose escalation and dose expansion) and phase II (cohort expansion) study in Chinese patients with advanced solid tumors. A pooled analysis of the two studies evaluated the safety and efficacy of JSKN003 in patients with platinum-resistant ovarian cancer. Results: As of July 15, 2024, 50 patients with PROC had received JSKN003 across five dose levels, among which 2 patients at the dose of 4.2mg/kg, 2 patients at the dose of 5.2mg/kg, 44 patients at the dose of 6.3mg/kg, 1 patient at the dose of 7.3mg/kg, and 1 patient at the dose of 8.4mg/kg. Among the enrolled 50 patients based on the central laboratory testing, there were 17 patients with HER2 expression (IHC 1+, 2+ and 3+) (only 2 patients with HER2 IHC 3+), 17 patients with IHC 0, and 16 patients had no HER2 results because they had not been tested by July 15. 28 patients (56.0%) had at least three prior lines of systemic treatment, 37 patients (74.0%) had received bevacizumab treatment, and 28 patients (56.0%) had received PARP inhibitor treatment. The median duration of treatment was 12.4 weeks (range: 0.7 - 51.0 weeks), with 32 patients (64.0%) remained on treatment to the data cut-off date. Safety: Among all the enrolled 50 patients, 3 patients experienced interstitial lung disease (ILD)/pneumonitis. 5 patients (10.0%) experienced grade 3 treatment-related adverse events (TRAEs), with the most common being diarrhea (2.0%) and anemia (2.0%). No TRAEs led to death. Efficacy: Among the 44 efficacy evaluable patients who had at least one post-baseline tumor assessment, the objective response rate (ORR) was 56.8% (95% CI: 41.0, 71.7), with 39 patients (88.6%) showing tumor shrinkage. The ORR in patients with centrally confirmed HER2 IHC 0 and HER2 expression (IHC 1+, 2+ and 3+) was 52.9% (95% CI: 27.8, 77.0) and 68.8% (95% CI: 41.3, 89.0), respectively. For 33 patients who received prior bevacizumab treatment the ORR was 54.5% (95% CI: 36.4, 71.9), for 26 patients who received prior PARP inhibitor treatment the ORR was 46.2% (95% CI: 26.6, 66.6). Conclusions: JSKN003 exhibited a favorable tolerability and safety profile, with lower occurrence of gastrointestinal toxicity and hemotoxicity. JSKN003 demonstrated promising efficacy in heavily pretreated patients with PROC, irrespective of HER2 expression. These data support further clinical exploration of JSKN003 in this population. Methods: Results of the pooled analysis of patients enrolled in JSKN003-101 (NCT05494918) conducted in Australia and JSKN003-102 (NCT05744427) conducted in China with histologically documented HER2-positive (IHC 3+) solid tumors, were presented at the ESMO Congress 2024. Patients who have failed prior standard therapy, were enrolled and received JSKN003 monotherapy to evaluate safety and efficacy of JSKN003. Results: As of July 15, 2024, 29 patients (9 colorectal cancer, 6 gastric cancer, 4 biliary tract carcinoma, 3 esophageal carcinoma, 2 ovarian cancer, 1 head and neck cancer and 4 others) were enrolled and received JSKN003 monotherapy intravenously (Q3W). 12 patients (41.4%) had at least three prior lines of systemic treatment, 14 patients (48.3%) had received anti-HER2 treatment and 7 patients (24.1%) had received anti-HER2 ADC treatment. The median duration of treatment was 23.6 weeks (range: 4.7~52.0 weeks), and 14 patients remained on treatment to the data cut-off date. Efficacy: Among the 28 efficacy evaluable patients, the ORR and disease control rate (DCR) were 75.0% and 89.3%, respectively. For 7 patients who received prior anti-HER2 ADC, the ORR was 71.4%. The ORR of gastric cancer and colorectal cancer were 83.3% (5/6) and 66.7% (6/9) respectively. Safety: Among all the enrolled 29 patients, 6 patients (20.7%) experienced grade 3 or higher TRAEs, including neutrophil count decreased (6.9%), vomiting (3.4%), fatigue (3.4%), white blood cell decreased (3.4%) and appetite decreased (3.4%). No TRAEs led to death. Conclusions: JSKN003 exhibited a favorable tolerability and safety profile, with a lower incidence of hematological toxicity. Encouraging antitumor activity was observed in heavily pretreated patients with advanced HER2-positive solid tumors. Promising ORR was observed in patients with high HER2 expressing gastrointestinal tumors, which supports further clinical evaluation of JSKN003 in this field.
