• 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.