1425P - Efficacy and safety of KN026 in combination with chemotherapy in patients (pts) with unresectable or metastatic HER2 positive gastric or gastroesophageal cancers (GC/GEJC) after first-line treatment with a trastuzumab-containing regimen

Background

Developing new later-line treatment in HER2-positive GC/GEJC seemed more challenging. KN026 is a novel HER2-targeted bispecific antibody that binds two distinct domains of HER2. Previous study demonstrated KN026 monotherapy had shown promising efficacy in pts with GC/GEJC.

Methods

In this multicenter, open-label, phase II study, pts with HER2 positive GC/GEJC after first-line treatment with a trastuzumab-containing regimen were assigned to receive KN026 (30 mg/kg, D1, Q3W) + paclitaxel (175 mg/m², D1, Q3W) or irinotecan (125 mg/m², D1 and D8, Q3W) at investigators' discretion based on previous treatment. Primary endpoint were safety and objective response rate (ORR) by independent review committee (IRC).

Results

At data cutoff (March 26, 2024), 39 pts were enrolled and received at least one dose of treatment. The median (range) age was 59.0 years (34-78). HER 3+ staining was observed in 34 pts (87.2%). 35 and 37 pts were eligible for response evaluation by IRC and investigators, respectively. The confirmed ORR and disease control rate (DCR) by IRC were 40.0% (14 PRs, 95% CI 23.9-57.9) and 80.0% (8 SDs, 95% CI 63.1-91.6). The confirmed ORR and DCR by investigators were 45.9% (17 PRs, 95% CI 29.5-63.1) and 81.1% (13 SDs, 95% CI 64.8-92.0). Median time to response and duration of response were 1.38 months (interquartile range 1.38-1.45) and 11.7 months (95% CI 5.98-NA). Median progression-free survival and overall survival were 8.6 months (95% CI 3.78-13.11) and 13.2 months (10.58-20.53). The most common ≥ grade 3 TRAEs (≥ 5%) were neutropenia (33.3%), leukopenia (28.2%), anemia (17.9%), fatigue (10.3%), diarrhea (7.7%), lymphocytopenia (5.1%), frebrile neutropenia (5.1%), hypokalemia (5.1%), and cough (5.1%). No treatment-related deaths occurred. No new safety signal was observed.

Conclusions

KN026 in combination with chemotherapy have promising anti-tumor efficacy in pts with HER2 positive GC/GEJC after first-line treatment, with a well-tolerated safety profile. Phase III study of KN026 in combination with chemotherapy is ongoing.

Clinical trial identification

NCT05427383.

Editorial acknowledgement

Legal entity responsible for the study

CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.

Funding

CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.

Disclosure

Y. Liu: Financial Interests, Personal, Full or part-time Employment: CSPC Pharmaceutical Group Co., Ltd. K. Zou, D. Wang, Y. Xie: Financial Interests, Personal, Full or part-time Employment: CSPC Pharmaceutical Group Limited. All other authors have declared no conflicts of interest.