At the ESMO Congress 2026, Xiaohua Wu (Shanghai, China) presented findings from the phase I/II JSKN033-102 trial (NCT06770881), evaluating a first-in-class subcutaneous combination of a HER2-targeted antibody–drug conjugate (ADC) and a PD-L1 inhibitor in patients with previously treated advanced cervical cancer.
The investigational therapy, JSKN033, demonstrated promising antitumor activity, achieving an objective response rate (ORR) of 52.9% at the recommended phase II dose of 8.4 mg/kg.
Methods
JSKN033 is a fixed-dose subcutaneous co-formulation combining JSKN003, a biparatopic anti-HER2 ADC, with envafolimab, a PD-L1 inhibitor.
The phase I/II study enrolled 64 patients with previously treated advanced cervical cancer who received JSKN033 across different dosing schedules at 6.7 mg/kg or 8.4 mg/kg.
The median patient age was 54 years. Among participants, 75% had previously received immunotherapy, 56.3% bevacizumab, and 31.3% at least three prior lines of systemic therapy.
Most patients (71.9%) had HER2 IHC 0 tumors, while 50% had PD-L1-negative disease (CPS below 1).
Key Takeaways
At the March 20, 2026, data cutoff, JSKN033 demonstrated encouraging efficacy, particularly at the 8.4 mg/kg dose.
- Objective response rate: 52.9% (18/34) at 8.4 mg/kg, compared with 17.9% (5/28) at 6.7 mg/kg.
Disease control rate: 88.2% at 8.4 mg/kg. - Median progression-free survival: 7.2 months at 8.4 mg/kg.
- Subgroup activity: Antitumor activity was reported across subgroups defined by HER2 and PD-L1 expression, prior immunotherapy, and bevacizumab exposure.
- Safety: Grade ≥3 treatment-related adverse events occurred in 26.6% of patients. Injection-site reactions were the most common adverse events (95.3%), with 1.6% being grade ≥3.
- Treatment discontinuation: No treatment-related adverse events led to dose reduction, treatment discontinuation, or death. One case of interstitial lung disease was reported.
Conclusion
JSKN033 demonstrated promising antitumor activity and a manageable preliminary safety profile in patients with previously treated advanced cervical cancer, including those previously exposed to immunotherapy.
The reported activity across HER2 and PD-L1 expression subgroups is particularly noteworthy, although larger studies are needed to determine whether these biomarkers influence treatment response.
The 8.4 mg/kg dose was selected as the recommended phase II dose, supporting further clinical development. Longer follow-up and additional studies will be necessary to confirm the durability of response, long-term safety, and clinical benefit of this novel subcutaneous combination.
