• Results from the phase I part of JSKN003-102 was reported at this ASCO Annual Meeting.

• JSKN003 exhibited a favorable tolerability and manageable safety profile in heavily pretreated patients with advanced/metastatic solid tumors and demonstrated encouraging antitumor activity during dose escalation phase.

SUZHOU, China, June 3, 2024 /PRNewswire/ -- Alphamab Oncology (stock code: 9966.HK) announced that data from the clinical study conducted in China (JSKN003-102) of anti-HER2 bispecific antibody-drug conjugate (ADC) JSKN003 for the treatment of HER2-expressing advanced solid tumors, were presented for the first time at the 2024 Annual Meeting of American Society of Clinical Oncology (2024 ASCO Annual Meeting).

Title: Evaluation of the safety, pharmacokinetics, and efficacy of JSKN003 in patients with advanced solid tumors: A phase I/II clinical study
Abstract Number for Publication: 3031
Session Type and Title: Poster Session - Developmental Therapeutics -Molecularly Targeted Agents and Tumor Biology
Leading PI: Prof. Jian Zhang, Fudan University Shanghai Cancer Center
Session Date and Time: 6/1/2024 9:00 AM-12:00 PM CDT

JSKN003, an anti-HER2 bispecific antibody-drug conjugate (bis-ADC), developed inhouse with proprietary Glycan-specific conjugation platform, shows better serum stability which may lead to a broader therapeutic window. The data of the phase I clinical trial conducted in Australia presented at the 2024 Annual Meeting of American Association for Cancer Research (AACR) in April demonstrated favorable tolerability, safety profile and encouraging preliminary anti-tumor activity. Multiple clinical studies of JSKN003 are currently being conducted in Australia and China, and we are also actively making the progress in its pivotal clinical trial in advanced HER2 low-expression breast cancer in China.

METHODS

JSKN003-102 (NCT05744427) is a phase I (dose escalation and expansion) and phase II (cohort expansion) clinical study in Chinese patients with advanced solid tumors. Patients with confirmed pathological records of unresectable locally advanced or metastatic solid tumors with HER2 expression (IHC≥1+) or gene mutation (HER2 exon 19 or 20 mutation) who failed standard therapy, cannot tolerate standard therapy, or lack of effective treatment were enrolled. The objectives were safety, pharmacokinetics (PK), preliminary antitumor activity of JSKN003 and to determine the maximum tolerated dose (MTD) or the recommended phase II dose (RP2D). Dose-escalation part adopts BOIN design across 7 dose levels (1.0 - 8.4 mg/kg, Q3W).

RESULTS

As of April 5, 2024, 46 patients (25 breast cancers, 11 gastric cancers, 8 colorectal cancers, 1 lung cancer, and 1 ovarian cancer) were enrolled and received JSKN003 across 6 dose levels (2.1 - 8.4mg/kg, Q3W) in phase I part (1.0mg/kg was exempted). 34 patients (73.9%) had received ≥ 3 lines prior treatment, 28 (60.9%) and 21 (45.7%) patients had received anti-HER2 and anti-HER2 ADC treatment, respectively.

Safety: The median duration of treatment was 19.2 (range, 3.0 - 52.0) weeks, and 26 patients (56.5%) remained on treatment. Treatment-related adverse events (TRAEs) occurred in 46 patients. Only 9 patients (19.6%) experienced grade 3 TRAEs and no ＞grade 3 TRAE occurred. 3 patients (6.5%) had treatment related SAEs (1 patient grade 3 nausea, 2 patients grand 2 ILD). No DLT event and no TRAE led to discontinuation.

Pharmacokinetics (PK): Following a single dose, exposures (C_max and AUC) of JSKN003 increased with dose escalation and the mean half-life of JSKN003 is approximately 5 days for 6.3 mg/kg. No significant accumulation was observed after 4 cycles treatment. The systemic exposure of free payload was significantly lower than JSKN003, demonstrating the stability of JSKN003 in circulation.

Efficacy: Among the 45 efficacy evaluable patients, the ORR and DCR were 51.1% (95%CI: 35.8, 66.3) and 93.3% (95%CI: 81.7, 98.6), respectively. The ORR in patients with IHC 1+, 2+ and 3+ was 14.3% (95% CI: 0.4, 57.9), 35.0% (95% CI: 15.4, 59.2), and 83.3% (95% CI: 58.6, 96.4), respectively. For 28 patients who received prior anti-HER2 the ORR was 57.1% (95% CI: 37.2, 75.5), for 21 patients who received prior anti-HER2 ADC the ORR was 57.1% (95% CI: 34.0, 78.2). The results still showed efficacy signals in patients with previous anti-HER2 ADC treatment.

For HER2 positive (HER2 IHC 3+, or IHC 2+ & FISH +) breast cancer and gastric cancer, the ORR was 73.3% (95% CI: 44.9, 92.2) in 15 patients and 80% (95% CI: 28.4, 99.5) in 5 patients, respectively. For HER2-low (HER2 IHC 1+, or IHC 2+ & FISH -) breast cancer and gastric cancer, the ORR was 33.3% (95% CI: 7.5, 70.1) in 9 patients and 20% (95% CI: 0.5, 71.6) in 5 patients, respectively.

CONCLUSIONS

JSKN003 exhibited a favorable tolerability and safety profile in heavily pretreated patients with advanced/metastatic solid tumors: No DLT was observed, MTD has not been reached yet. Hemotoxicity and ILD (2/46, grade 2) occurred at very low frequency. Encouraging antitumor activity was observed during dose escalation phase: The ORR was 51.1% in all efficacy evaluable patients across HER2 low and HER2 positive populations. For prior anti-HER2 treated patients, the ORR was 57.1%. For breast cancer, the ORR was 73.3% in 15 HER2 positive patients and 33.3% in 9 HER2 low patients, respectively.

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 of JSKN003 are currently being conducted in Australia and China, and we are also actively making the progress in its pivotal clinical trial in advanced HER2 low-expression breast cancer in China.

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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