649P - Phase I study of SHR-A2102, a nectin-4 targeted ADC, in patients with advanced solid tumors

Background

Nectin-4 is a cell adhesion molecule that serves as an attractive therapeutic target for ADCs, due to its high expression in a variety of solid tumors. SHR-A2102 is a novel ADC comprised of a fully humanized IgG1 mAb against nectin-4, a cleavable linker, and a topoisomerase I inhibitor payload. Here we present results of the dose escalation (D-ESC) and dose expansion (D-EXP) parts of a phase 1 study of SHR-A2102 for treating solid tumors.

Methods

Patients (pts) with nectin-4 positive, locally advanced unresectable or metastatic solid tumors, who had failed or were intolerant to standard therapies or had no standard treatment, were given SHR-A2102 intravenously Q3W. Primary objectives were to assess safety and tolerability.

Results

As of Apr 9, 2024, 38 pts were enrolled (median age: 61 yrs; ≥3 lines of prior therapies: 60.5%; prior ICI: 78.9%). During D-ESC, 17 pts received SHR-A2102 at 2 to 10 mg/kg. Only 1 pt in the 10 mg/kg group experienced a DLT (grade 4 decreased platelet count), and MTD was not yet reached. During D-EXP, additional 10 and 11 pts were given SHR-A2102 at 6 and 8 mg/kg, respectively. Overall, grade 3/4 TRAEs occurred in 42.1% (16/38) of pts, with the most common (≥10%) being decreased WBC count (21.1%), anemia (18.4%), decreased neutrophil count (15.8%), and decreased lymphocyte count (13.2%). No treatment-related deaths occurred. Among 30 pts evaluable for tumor response, ORR was 23.3% and DCR was 76.7% (Table). In 16 heavily pretreated NSCLC pts evaluable for tumor response, ORR was 31.3% (non-sq, 50.0%; sq, 12.5%) and DCR was 87.5% (non-sq, 75.0%; sq, 100.0%; Table). Table: 649P

Anti-tumor activity

Non-sq, non-squamous; sq, squamous.

Conclusions

SHR-A2102 showed a manageable safety profile and promising anti-tumor activity. Indication-specific cohorts are being recruited during the efficacy expansion part.

Clinical trial identification

NCT05701709; Release date: Jan 27, 2023.

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

X. Li, Y. Huang, L. Song: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals. All other authors have declared no conflicts of interest.