30.3 C
Vientiane
Thursday, June 5, 2025
spot_img

Alphamab Oncology Presented Multiple Clinical Data of Anti-HER2 Biparatopic ADC JSKN003 at the 2025 ASCO Annual Meeting

This Week

SUZHOU, China, June 3, 2025 /PRNewswire/ — Alphamab Oncology (stock code: 9966.HK) announced that multiple clinical data updates for anti-HER2 biparatopic antibody-drug conjugate (ADC) JSKN003 were presented as posters at the 2025 Annual Meeting of American Society of Clinical Oncology (2025 ASCO Annual Meeting) from May 30 to June 3, 2025, in Chicago, IL, U.S.. The results covered platinum-resistant ovarian cancer, HER2-positive breast cancer, and HER2-overexpressing gastrointestinal tumors.

Title: JSKN003, a biparatopic anti-HER2 antibody drug conjugate (ADC), in the treatment of platinum-resistant ovarian cancer (PROC): Updated findings from two clinical trials
Abstract Number for Publication: 5557
Session Type and Title: Poster Session – Gynecologic Cancer
Session Date and Time: 6/1/2025 9:00 AM-12:00 PM CDT
Presenter: Xiaohua Wu, Fudan University Shanghai Cancer Center

Methods

JSKN003-101 (NCT05494918) is a Phase I study in Australia and JSKN003-102 (NCT05744427) is a Phase I/II study in China. Both trials enrolled patients with advanced solid tumors who were to receive JSKN003 monotherapy at various dose levels. Pooled results have demonstrated that JSKN003 monotherapy has promising efficacy signals in patients with PROC, and the efficacy was observed across patients with (IHC 1+/2+/3+) or without (IHC 0) HER2 expression, with or without prior bevacizumab and prior PARP inhibitor. Preliminary data from the pooled analysis of these two studies were presented at the 2024 European Society for Medical Oncology (ESMO) Congress for the first time. The latest findings for non-primary platinum-refractory PROC patients at a longer follow-up time were reported at this ASCO Annual Meeting.

Results

As of February 28, 2025, 46 PROC patients were enrolled and received JSKN003 every three weeks across five doses levels, among which 2 patients at the dose of 4.2 mg/kg, 2 patients at the dose of 5.2 mg/kg, 40 patients at the dose of 6.3 mg/kg (RP2D), 1 patient at the dose of 7.3mg/kg, and 1 patient at the dose of 8.4mg/kg.

Efficacy: With a median follow-up time of 9.3 months, 46 patients were efficacy evaluable. 42 patients (91.3%) exhibited tumor shrinkage. The objective response rate (ORR) was 63.0%, the median progression-free survival (PFS) was 7.7 months, and the 9-month overall survival (OS) rate was 89.9%. Efficacy was observed across different HER2-expression subgroups. The ORR was 52.4% and the median PFS was 6.6 months in patients with HER2 IHC 0. The ORR reached 72.2% and the median PFS was 9.4 months in patients with HER2 expression (IHC 1+/2+/3+).

Safety: Grade 3-4 treatment-related adverse events (TRAEs) occurred in 9 patients (19.6%). Serious TRAEs were reported in 6 patients (13.0%). No TRAEs leading to death. Interstitial lung disease (ILD) was observed in 5 patients (10.9%), all were Grade 1/2.

Conclusions

With extended follow-up, JSKN003 demonstrated robust PFS improvement in PROC, along with early signals of OS benefit. A confirmatory trial (JSKN003-306, NCT06751485) is currently enrolling all comers regardless of HER2 expression to validate JSKN003 as a treatment option for this patient population.

Title: JSKN003, a biparatopic HER2-targeting ADC, in heavily pretreated HER2-positive breast cancer: A pooled analysis of early-phase studies
Abstract Number for Publication: 1028
Session Type and Title: Poster Session – Breast Cancer – Metastatic
Session Date and Time: 6/2/2025 9:00 AM-12:00 PM CDT
Presenter: Yiqun Du, Fudan University Shanghai Cancer Center

Methods

The pooled analysis was performed to evaluate the efficacy and safety of JSKN003 in HER2-positive (IHC 3+ or 2+/ISH+) advanced breast cancer from the Phase I clinical trial (JSKN003-101, NCT05494918) in Australia and the Phase I/II clinical trial (JSKN003-102, NCT05744427) in China.

Results

As of February 28, 2025, the median follow-up duration was 6.1 months. A total of 88 patients with HER2-positive breast cancer were enrolled, with the majority receiving 6.3 mg/kg or 8.4 mg/kg doses. The median age was 55 years (range: 32-79), with 77.3% ECOG PS 1. All patients had stage IV disease, with 76.1% having visceral metastases. All patients had prior anti-HER2 therapy, including 85.2% with prior ADCs or TKIs, and 55.7% having at least three prior lines treatment.

Efficacy: A total of 80 T-DXd-naïve patients were enrolled, of whom 75 were evaluable for efficacy. In this population (N=75), JSKN003 demonstrated a confirmed ORR of 54.7% (95% CI: 42.7-66.2). The disease control rate (DCR) and clinical benefit rate (CBR) were 94.7% and 66.7%, respectively.

Among 30 patients treated at the RP2D of 6.3 mg/kg, the confirmed ORR was 73.3%, and CBR reached 83.3%. Subgroup analyses by line of therapy showed ORRs of 66.7% in the prior first line group of 15 patients and 63.2% in the prior second line group of 19 patients, respectively.

In addition, 8 patients who had previously received T-DXd were enrolled, among whom 7 had evaluable efficacy data. One patient achieved a partial response (PR), four had stable disease (SD), and tumor shrinkage was observed in four patients. These patients were analyzed separately for exploratory purposes.

The median duration of response (DoR) in the overall population was 18.4 months (95% CI: 9.9-NE). Median PFS was not mature at the time of data cutoff. The 3-month and 6-month PFS rates were 88.4% (95% CI: 78.8–93.8) and 75.4% (95% CI: 62.3–84.4), respectively.

Safety: 15.9% of patients experienced Grade 3 or higher TRAEs. Serious TRAEs were reported in 5.7% of patients. Dose reductions due to TRAEs occurred in 12.5% of patients, and one patient discontinued due to a TRAE. No TRAEs led to death. The most common TRAEs (≥20%) were nausea, increased alanine aminotransferase, decreased white blood cell count, vomiting, anemia, decreased appetite, thrombocytopenia, fatigue, neutropenia, and diarrhea. ILD was reported in 4 patients (4.5%), mostly Grade 1-2; one case was Grade 3.

Conclusions

JSKN003 demonstrated promising antitumor activity and manageable safety in heavily pretreated HER2-positive breast cancer, including patients previously treated with T-DXd. Its biparatopic HER2 antibody design may enhance target binding and contribute to the observed clinical benefit. A pivotal Phase III trial (JSKN003-301, NCT06846437) is ongoing to compare JSKN003 with T-DM1 in patients with HER2-positive advanced breast cancer who were previously treated with trastuzumab.

Title: A pooled analysis of JSKN003, a biparatopic anti-HER2 antibody conjugate (ADC), in patients with advanced HER2-overexpressing (IHC 3+) gastrointestinal tumors
Abstract Number for Publication: 3022
Session Type and Title: Poster Session – Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Session Date and Time: 6/2/2025 1:30 PM-4:30 PM CDT
Presenter: Dan Liu, Beijing Cancer Hospital

Methods

The pooled analysis was performed to evaluate the efficacy and safety of JSKN003 in HER2-overexpressing (IHC 3+) metastatic gastric cancer or gastroesophageal junction cancer (GC/GEJC) and colorectal cancer (CRC) patients from the Phase I clinical trial (JSKN003-101, NCT05494918) in Australia and the Phase I/II clinical trial (JSKN003-102, NCT05744427) in China.

Results

As of February 28, 2025, a total of 50 patients with HER2-overexpressing gastrointestinal tumors (27 patients in GC/GEJC and 23 patients in CRC) were enrolled and treated with JSKN003 monotherapy across 7 dose levels: 1 patient at the dose of 2.1 mg/kg, 1 patient at the dose of 4.2 mg/kg, 1 patient at the dose of 5.2 mg/kg, 43 patients at the dose of 6.3 mg/kg, 1 patient at the dose of 7.3 mg/kg, 2 patients at the dose of 8.4 mg/kg and 1 patient at the dose of 10.5 mg/kg. The median age was 60 years (range: 52-66), with 86.0% ECOG PS 1. Most patients were heavily pretreated: 38.0% had at least three lines of prior therapies, 68.0% received anti-HER2 therapy, 48.0% received Irinotecan.

Efficacy: Among 48 patients who had at least one tumor assessment after baseline, JSKN003 demonstrated the ORR of 62.5% and the DCR was 93.8%. Among 27 patients with GC/GEJC, the ORR was 63.0% and DCR reached 92.6%. Among 21 patients with CRC, the ORR was 61.9% and DCR reached 95.2%. Among twenty patients with BRAF V600E-wild type, the ORR was 65.0%.

Additionally, among 24 patients (4 patients in GC/GEJC and 20 patients in CRC) who were pretreated with irinotecan, the ORR achieved 58.3%.

The median DoR in GC/GEJC patients was 9.6 months (95% CI: 3.0-NE), while the median DoR in CRC patients was 12.1 months (95% CI: 5.8-NE). Median PFS was 9.6 months (95%CI: 4.3, 11.6) with 70.4% PFS rate at 6 months in GC/GEJC patients. Median PFS was 13.8 months (95% CI: 6.8, NE) with 88.9% PFS rate at 6 months in CRC patients.

Safety: 18.0% of patients experienced Grade 3 or higher TRAEs. Serious TRAEs were reported in 6.0% of patients. Dose reduction due to TRAEs occurred in 20.0% of patients and 16.3% at RP2D. No TEAEs led to discontinuation or death. The most common TRAEs (≥20%) were nausea, diarrhea, decreased appetite, decreased white blood cell count, anemia, fatigue, decreased neutrophil count, decreased platelet count and vomiting. ILD was reported in 3 patients (6.0%), with Grade 1 in 2 patients and Grade 2 in 1 patient.

Conclusions

JSKN003 demonstrated promising efficacy in heavily pretreated HER2-overexpressing (IHC3+) gastrointestinal tumors including patients previously treated with irinotecan, with a manageable and predictable safety profile. The HER2 biparatopic ADC design may contribute to the observed clinical benefit.

About JSKN003

JSKN003 is a bispecific ADC developed based on KN026 using Alphamab’s proprietary glycan-specific conjugation platform. JSKN003 can bind HER2 on the surface of tumor cells and release topoisomerase I inhibitors (TOPIi) through cellular endocytosis, thereby exerting anti-tumor effects. Compared with its ADC counterparts, JSKN003 demonstrated better serum stability and stronger bystander effect, which effectively expands the therapeutic window.

Results of multiple clinical studies at various stages of JSKN003 in China and Australia have demonstrated favorable safety profile, with promising efficacy of JSKN003 in heavily pretreated patients with advanced solid tumors, especially in patients with platinum-resistant ovarian cancer (PROC), HER2-expressing breast cancer (BC), or high HER2-expressing solid tumors. JSKN003 was granted breakthrough therapy designation by CDE. The designation is for the treatment of platinum-resistant recurrent epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. Three Phase III clinical studies of JSKN003 for the treatment of HER2-low expressing BC, PROC, and HER2-positive BC as well as multiple exploratory Phase II clinical studies are currently undergoing smoothly.

In September 2024, the Company entered a licensing agreement with JMT-Bio Technology Co., Ltd. (“JMT-Bio”), a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. (“CSPC”) (stock code: 1093.HK), pursuant to which, JMT-Bio was granted the exclusive license and sublicense rights to develop, sell, offer for sale and commercialize JSKN003, for the treatment of tumor-related indications (the “Field”) in mainland China (excluding Hong Kong, Macau or Taiwan) (the “Territory”) and become the sole marketing authorization holder for JSKN003 for the Field in the Territory. Alphamab retains the sole right to supply JSKN003.

About Alphamab Oncology

Alphamab Oncology is an innovative biopharmaceutical company focusing on oncology therapeutics. By leveraging its proprietary core technology platforms including single-domain antibodies, bispecific antibodies, glycan-specific conjugation, linker-payload, dual-payload antibody conjugation, and subcutaneous high concentration formulation for biologics, the Company has established a product portfolio with differentiated innovation and global competitiveness, covering cutting-edge areas such as antibody-drug conjugates (ADCs), bispecific antibodies, and single-domain antibodies.

The Company has one product approved for marketing (Envafolimab, the world’s first subcutaneously injectable PD-(L)1 inhibitor), which has made a significant breakthrough in the convenience and accessibility of cancer treatment. Additionally, the Company has multiple bispecific antibodies and bispecific ADCs in clinical stage, while rapidly advancing the preclinical pipeline prioritizing bispecific ADCs and dual-payload ADCs. Multiple strategic collaborations based on innovative products or technology platforms have been established with partners such as CSPC, ArriVent, and Glenmark.

Our overarching mission is to make cancer manageable and curable by addressing unmet clinical needs in oncology. Alphamab Oncology is continuously dedicated to the development of effective, safe, and globally competitive anti-tumor drugs, delivering China-innovated cancer therapies to benefit patients worldwide.

Latest article