On October 20, 2025 Alphamab Oncology (stock code: 9966.HK) reported that two latest clinical data on biparatopic HER2-targeting antibody-drug conjugate (ADC) JSKN003 for the treatment of primary platinum-refractory ovarian cancer (OC) and HER2-positive metastatic colorectal cancer (mCRC), along with the confirmatory study design of the phase III study of JSKN003 versus physician’s choice of chemotherapy in platinum-resistant ovarian cancer (PROC) were presented as posters at the 2025 European Society for Medical Oncology Congress (ESMO Congress 2025) from October 17 to 21, 2025, in Berlin, Germany (Press release, Alphamab, OCT 20, 2025, View Source [SID1234656988]).
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Title: Biparatopic anti-HER2 antibody drug conjugate (ADC) JSKN003 in the treatment of primary platinum-refractory ovarian cancer (OC)
Presentation Number: 1079P
Onsite Poster display date: Saturday, 18 October 2025
First author: Xiaohua Wu, Fudan University Shanghai Cancer Center
Speaker: Jiajia Li, Fudan University Shanghai Cancer Center
METHODS
Therapies represented by ADCs have made certain progress in treating platinum-resistant ovarian cancer (PROC), but not for primary platinum-refractory disease (defined as disease that progressed within 3 months after the last dose of first-line platinum-containing therapy) that were excluded from most of trials. Novel therapeutic options are urgently needed for this patient population with poorer prognosis compared to those who are not primary platinum-refractory. JSKN003-102 (NCT05744427) is a phase I/II trial conducted in China, enrolling patients with advanced solid tumors to receive JSKN003 monotherapy. The findings of JSKN003 in treating patients with primary platinum-refractory OC were reported at this ESMO (Free ESMO Whitepaper) Congress.
RESULTS
As of June 13, 2025, a total of 26 patients with primary platinum-refractory OC were enrolled and received JSKN003 at 6.3 mg/kg every three weeks. The median age was 54 years, with 80.8% of them having ECOG PS 1. Among the patients, 15 patients were HER2-negative (IHC 0), 8 had HER2 expression (IHC 1+/2+/3+), with only one being IHC 3+), and 3 patients had no tumor sample available for assessment. All patients had prior treatments, of whom 84.6% had previously been treated with bevacizumab, 26.9% had received PARP inhibitors, and 57.7% had undergone two or more lines of systemic anti-tumor therapies. Additionally, 38.5% of the patients had liver metastases, while 26.9% had lung metastases.
Efficacy: As of June 13, 2025, 25 patients were efficacy evaluable. The overall response rate (ORR) was 32.0%, the disease control rate (DCR) was 72.0%, the median progression-free survival (PFS) was 4.1 months, and the 9-month overall survival (OS) rate was 65.4%. Efficacy was observed across different HER2 expression subgroups.
Safety: Grade 3 or above treatment related adverse events (TRAE) occurred in 15.4% of patients. Serious TRAEs were reported in 1 patient (3.8%). No TRAE led to death. Interstitial lung disease (ILD) was observed in 2 patients and both were Grade 1.
CONCLUSIONS
JSKN003 demonstrated promising efficacy and tolerability in patients with primary platinum-refractory OC who have limited treatment options. Efficacy was observed across different HER2 expression subgroups, offering new hope for this patient population.
Title: Efficacy and Safety of JSKN003, a Biparatopic anti-HER2 Antibody Drug Conjugate (ADC), in Patients with HER2-positive Metastatic Colorectal Cancer (mCRC)
Presentation Number: 806P
Onsite Poster display date: Sunday, 19 October 2025
First author & Speaker: Dan Liu, Peking University Cancer Hospital and Institute
METHODS
JSKN003-102 (NCT05744427) is a phase I (dose escalation and expansion) and phase II (cohort expansion) clinical study in Chinese patients with advanced/metastatic solid tumors. The efficacy and safety data of JSKN003 in HER2-positive (IHC 3+ or 2+/FISH+) mCRC patients were reported at this ESMO (Free ESMO Whitepaper) Congress.
RESULTS
As of June 30, 2025, a total of 33 patients with HER2-positive mCRC were enrolled and received JSKN003 every three weeks across 2 dose levels, among which 32 patients at the dose 6.3 mg/kg and 1 patient at the dose of 8.4 mg/kg. 69.7% of enrolled patients were male with a median age of 59 (range, 30-69). All enrolled patients were stage IV at screening and 54.5% with liver metastases. 5 (15.2%) patients harbored RAS/RAF mutations, including 1 case of BRAF V600E mutation. All patients were heavily pretreated, and 42.4% had received three or more lines of prior anti-tumor treatments.
Efficacy: 32 patients were efficacy evaluable. The ORR was 68.8%, the DCR was 96.9%. Additionally, among 31 BRAF V600E wild-type patients, the ORR was 71.0%, the DCR was 100%, and median duration of response (DoR) was 9.89 months (95%CI, 5.78 to NE), the median PFS achieved 11.04 months (95%CI, 6.9 to 14.03), with a 9-month PFS rate of 66.6%.
Safety: The median follow-up time was 9.26 months (95%CI: 5.82, 12.35). 7 patients (21.2%) experienced Grade 3 or above TRAEs. There were no TRAEs led to discontinuation or death. Overall, the most common TRAEs were diarrhea and nausea, most of which were Grade 1-2. ILD was reported in 4 patients (12.1%), which were Grade 1-2.
CONCLUSIONS
JSKN003 demonstrated promising efficacy in heavily pretreated HER2-positive CRC with a manageable and predictable safety profile. The biparatopic HER2 antibody design may enhance target binding and contribute to the observed clinical benefit.
Title: Phase III study of JSKN003, a biparatopic anti-HER2 antibody-drug conjugate (ADC), versus physician’s choice of chemotherapy in platinum-resistant ovarian cancer (PROC): JSKN003-306
Presentation Number: 1219TiP
Onsite Poster display date: Saturday, 18 October 2025
First author & Speaker: Lingying Wu, Cancer Hospital Chinese Academy of Medical Sciences
BACKGROUND
Platinum-resistant ovarian cancer (PROC) is known for low efficacy to non-platinum single-agent chemotherapy with or without bevacizumab, the standard-of-care (SOC), with an ORR of 15%, a PFS of 3 months, and an OS of 12 months, posing a significant therapeutic challenge.
Results from the Phase I clinical study JSKN003-101 (NCT05494918) in Australia and the Phase I/II clinical study JSKN003-102 (NCT05744427) in China have demonstrated promising efficacy of JSKN003 monotherapy in PROC. Detailed data were presented at the 2024 ESMO (Free ESMO Whitepaper) Congress for the first time and subsequently updated at the 2025 Annual Meeting of American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper). As of February 28, 2025, 46 PROC patients were enrolled and received JSKN003 every three weeks. In 46 efficacy-evaluable patients, 45.7% were HER2 no-expressing (IHC 0). 91.3% of patients exhibited tumor shrinkage, the ORR was 63.0%, the median PFS was 7.7 months and the 9-month OS rate was 89.9%. In HER2 expressing (IHC 1+/2+/3+) patients, the ORR and median PFS were 72.2% and 9.4 months, respectively.
Based on the pooled analysis of the two clinical studies, JSKN003 monotherapy has been granted breakthrough therapy designation for the treatment of PROC by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). So far, JSKN003 is the only anti-HER2 ADC to receive this designation without HER2 expression restrictions.
STUDY DESIGN
JSKN003-306 (NCT06751485) is randomized, open-label, parallel-controlled, multi-center Phase III clinical study, enrolling patients with recurrent platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancer, irrespective of HER2 expression. Key inclusion criteria include: age≥18 years; having received 1 to 4 prior lines of systemic anti-tumor therapy; disease progression within 6 months after the last dose of platinum-base chemotherapy; an ECOG PS of 0-1; adequate organ function; and measurable disease by RECIST v1.1. Key exclusion criteria include: prior TOPli or TOPli-containing ADC; active central nervous system metastases; interstitial lung disease (ILD); or uncontrollable comorbidities.
Patients will be randomized 1:1 and stratified by platinum-free interval (≤3 months vs. 3 to 6 months), number of prior lines of therapy (1/2 lines vs. 3/4 lines), and HER2 status (expressing vs. non-expressing) as assessed by a central laboratory. The experimental group will receive JSKN003 at 6.3 mg/kg once every 3 weeks, while the control group will receive the investigator’s choice of chemotherapy (paclitaxel, liposomal doxorubicin, or topotecan). The primary endpoints are PFS by blind independent central review (BICR) as per RECIST v1.1 and OS. Secondary endpoints include other efficacy outcomes assessed by BICR (ORR, DoR, DCR), investigator-assessed efficacy endpoints, safety, and others.
The JSKN003-306 study plans to enroll 556 patients across 80 sites in China. The first patient was successfully dosed in February 2025, and the study is currently in the patient enrollment phase. This study aims to further validate the superiority of JSKN003 over current therapies, potentially representing a breakthrough in treating PROC.
About JSKN003
JSKN003 is Alphamab Oncology’s first bispecific ADC, developed based on HER2-targeting bsAb KN026, and utilizing the proprietary glycan-specific conjugation platform. It binds to two HER2 epitopes on tumor cells and release topoisomerase I inhibitors (TOPIi) through cellular endocytosis, exerting anti-tumor effects. Compared to similar ADCs, JSKN003 demonstrates better serum stability, reduced hematological toxicity, and stronger tumor inhibition and bystander effect, resulting in significantly wider therapeutic window.
Clinical data in heavily pretreated advanced solid tumors have shown high-security profile, with promising efficacy of JSKN003, particularly in platinum-resistant ovarian cancer (PROC), HER2-high/low breast cancer (BC), HER2-positive colorectal cancer (CRC)/ gastric cancer (GC) and other HER2-expressing tumors. JSKN003 was granted breakthrough therapy designation by CDE for platinum-resistant recurrent epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer and HER2-positive advanced colorectal cancer that has failed prior oxaliplatin, fluorouracil, and irinotecan therapy. It has also been granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) for GC and gastroesophageal junction cancer (GEJ). Three Phase III trials in HER2-low expressing BC, PROC, and HER2-positive BC and multiple Phase II studies are underway.
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). JMT-Bio was granted the exclusive license and sublicense rights to develop, sell, offer for sale and commercialize JSKN003, for tumor-related indications in mainland China (excluding Hong Kong, Macau or Taiwan). Alphamab retains exclusive production rights for JSKN003.