Alphamab Oncology to Present Phase 1 Data on Bispecific ADC JSKN016 in HER2-Negative Breast Cancer at ASCO 2026

Alphamab Oncology will present early clinical findings from its investigational bispecific antibody-drug conjugate (ADC), JSKN016, at ASCO 2026, offering initial insight into its activity in HER2-negative breast cancer, a historically difficult-to-treat disease subset with limited targeted options.

The data derive from the Phase 1 JSKN016-101, a first-in-human, dose-escalation and expansion trial conducted in China in patients with advanced solid tumors.¹ The ASCO presentation will highlight results from the HER2-negative breast cancer cohort, including patients who have received multiple prior lines of therapy.

Dual-target strategy built on TROP2 and HER3 biology

JSKN016 is designed as a first-in-class bispecific ADC targeting both TROP2 and HER3, two receptors implicated in tumor proliferation, survival signaling, and resistance to therapy. By engaging two tumor-associated antigens simultaneously, the molecule aims to increase tumor selectivity while improving intracellular drug delivery.

Once bound to cancer cells, the ADC is internalized and releases a topoisomerase I inhibitor payload, triggering DNA damage and tumor cell death. According to Alphamab Oncology, early clinical observations show

encouraging antitumor activity alongside a manageable safety profile, even in heavily pretreated patients, including those with triple-negative breast cancer (TNBC).²

Engineering approach emphasizes stability and precision

A key feature of JSKN016 is its site-specific glycosylation conjugation technology, which produces a homogeneous drug-to-antibody ratio of 4. This controlled structure is intended to enhance pharmacokinetic stability and reduce off-target toxicity, a known limitation of earlier-generation ADCs.

This design reflects broader industry efforts to refine ADC platforms for improved therapeutic windows, particularly in solid tumors where safety and efficacy must be tightly balanced.

The study will be presented by principal investigator Herui Yao of Sun Yat-sen Memorial Hospital, a leading clinical site involved in early-phase oncology research.

Expansion strategy moves toward combinations and earlier lines

Beyond monotherapy evaluation, JSKN016 is being actively studied in combination with chemotherapy, immunotherapy, and targeted therapies across multiple tumor types. A Phase 3 program in TNBC is also underway, signaling the company’s intent to advance the asset into earlier lines of treatment and broader clinical settings.

This development strategy reflects a growing trend in ADC research: moving beyond single-agent late-line use toward combination regimens that integrate immune modulation and targeted therapies.

Broader implications for HER2-negative breast cancer

The ASCO 2026 presentation arrives amid continued expansion of ADCs into breast cancer subtypes beyond HER2-positive disease. HER2-negative breast cancer—including hormone receptor-positive and triple-negative subtypes—remains a major area of unmet need, particularly in patients who progress after standard chemotherapy and endocrine therapies.

If later-phase studies confirm the early signals observed in JSKN016-101, bispecific ADCs such as JSKN016 could represent a meaningful step forward in addressing resistance mechanisms that limit current treatment options.

References

1. To Evaluate the Phase I Clinical Study of JSKN016 in Chinese Patients With Advanced Malignant Solid Tumors. (2024 Sep 14). National Library of Medicine. Clinicaltrials.gov. https://clinicaltrials.gov/study/NCT06592417

2. Yao, H., Liu, J., Zeng, Y. (2025 May 28). First-in-human study of JSKN016, a bispecific anti-TROP2/HER3 antibody drug conjugate (ADC): Antitumor activity in patients (pts) with metastatic triple-negative breast cancer (mTNBC) and safety results. ASCO Publications. Journal of Clinical Oncology. https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e13138#C2462570.