The board of directors of Alphamab Oncology announced that the research results of a phase I clinical trial (study code: JSKN003-101) ("JSKN003-101") of JSKN003 in patients with advanced/metastatic solid tumors, have been presented during a poster session (poster board number: 7; abstract presentation number: CT179) at the 2024 AACR Annual Meeting, which is held from April 5, 2024 to April 10, 2024. JSKN003-101 is a first-in-human, open-label and multi-center phase I clinical trial divided into dose-escalation stage and dose-expansion stage in patients with advanced/metastatic solid tumors. As of March 15, 2024, among the 32 patients who were enrolled and received JSKN003 during the dose-escalation stage, 20 patients (62.5%) had at least three prior lines of systemic treatment.

Among all the enrolled patients, there were 15 patients (46.9%), 15 patients (46.9%) and two patients (6.3%) with an ECOG PS of 0, 1, and 2, respectively; there were nine patients (28.1%), 16 patients (50.0%) and seven patients (21.9%) with HER2 IHC 1+, IHC 2+, and IHC 3+, respectively; there were 15 patients (46.9%) with BC, five patients (15.6%) with ovarian cancer, three patients (9.4%) with bladder cancer, two patients (6.3%) with lung cancer, one patient (3.1%) with esophageal cancer, one patient (3.1%) with stomach cancer, one patient (3.1%) with head and neck cancer and other four patients (12.5%) with other types of tumors. The median duration of treatment was 20.4 weeks (range: 6 to 56 weeks), of which eight patients (25.0%) remained on treatment. Safety: Among all the enrolled patients, TRAEs occurred in 27 patients (84.4%), and TRAEs at grade 3 occurred in four patients (12.5%), including one patient at the dose of 4.2mg/kg (anemia, diarrhea), one patient at the dose of 7.3mg/kg (fatigue) and two patients at the dose of 8.4mg/kg (diarrhea, fatigue).

One patient at the dose of 7.3mg/kg experienced grade 2 ILD. 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%). In addition, the incidence of hematologic toxicity was low.

All the enrolled patients finished DLT observation period, without identifying any DLT events. Meanwhile, no TRAEs led to death or treatment discontinuation and the trial did not reach the MTD yet. Efficacy: The ORR and DCR were 56.3% (95% CI: 37.7% to 73.6%) and 90.6% (95% CI: 75.0% to 98.0%), respectively.

The ORR in patients with HER2 IHC 1+, IHC 2+ and IHC 3+ was 66.7% (6 of 9), 37.5% (6 of 16) and 85.7% (6 of 7), respectively. As for the efficacy of the HER2-positive BC and HER2-low expressing BC, the ORR was 100.0% (all five patients) and 50.0% (5 of 10), respectively. Pharmacokinetics: The exposures of JSKN003 increased with the dose escalated, and the mean half-life of JSKN003 is approximately 5 days for 6.3mg/kg.

Accumulation appeared following multiple doses, and the mean accumulation ratio was approximately 1.3 at the dose of 6.3mg/kg. The exposure of released payload was significantly lower than JSKN003, with Cmax being approximately 1.21ng/ml at the dose of 6.3mg/kg, demonstrating the stability of JSKN003 in circulation. Conclusions: JSKN003 demonstrated encouraging preliminary anti-tumor activity in patients with advanced/metastatic solid tumors who received prior multi-line treatment, and exhibited a favorable tolerability and safety profile with low occurrence of hemotoxicity and ILD (only one patient experienced grade 2 ILD).

As of March 15, 2024, all the enrolled patients finished DLT observation period, without identifying any DLT events nor reaching the MTD. JSKN003 is a biparatopic HER2-targeting ADC, of which a topoisomerase I inhibitor is linked to the N glycosylation site of the antibody KN026 (a recombinant humanized anti-HER2 bispecific antibody) via the glycosite-specific conjugation. The click reaction-based conjugation confers better serum stability than maleimide-Michael reaction-based conjugation.

The biparatopic HER2 targeting enables JSKN003 to have stronger internalization induction and bystander killing effect leading to potent anti-tumor activity in HER2 expression tumors. Currently, a phase I clinical trial in Australia and phase I/II clinical trials in China of JSKN003 are undergoing, a phase III clinical trial of JSKN003 in China is also being actively initiated.