609O - CLDN18.2 targeted antibody-drug conjugate (ADC), SHR-A1904, in patients (pts) with gastric/gastroesophageal junction cancer (GC/GEJC): A phase I study

Background

CLDN18.2 is a tight junction protein highly expressed in several tumors, especially GC/GEJC. SHR-A1904 is a novel ADC comprised of an IgG1 mAb targeting CLDN18.2, a cleavable linker, and a topoisomerase I inhibitor payload. We initiated a 3-part phase 1 study to assess SHR-A1904 in pts with advanced solid tumors who had failed standard therapies or had no standard treatment. Here, we present the findings in pts with CLDN18.2+ GC/GEJC.

Methods

During dose escalation, pts received SHR-A1904 at 0.6–8.0 mg/kg (Q3W IV) in an i3+3 design. During PK expansion, additional pts were enrolled at selected tolerable doses. During efficacy expansion, indication-specific cohorts were assessed at optimal dose(s). Primary objectives were to evaluate the safety and tolerability and determine the DLT, MTD, and RP2D.

Results

As of Mar 18, 2024, a total of 73 GC/GEJC pts were enrolled. 98.6% of pts had metastases, and 31.5% had received ≥3 lines of therapies (median, 2 [range, 1–5]). Three of the 29 pts enrolled during dose escalation reported DLTs, including 2 of 9 pts at 4.8 mg/kg (grade 3 febrile neutropenia and grade 3 increased blood bilirubin) and 1 of 6 pts at 6.0 mg/kg (grade 3 gastric mucosal lesion). MTD was not reached. 6.0 and 8.0 mg/kg were selected for expansions, and additional 44 pts were enrolled. Overall, grade ≥3 treatment-related AEs occurred in 53.4% (39/73) of pts, with the most common (≥10%) being decreased WBC count, decreased neutrophil count, and anemia. After a single dose, exposure of SHR-A1904 and total antibody increased approximately proportionally across 0.6–8.0 mg/kg. Mean t_1/2 of SHR-A1904 was 6.5 d at 6.0 mg/kg and 6.0 d at 8.0 mg/kg. Among the pts who had baseline and ≥1 post-baseline assessment, ORR and DCR were 55.6% (5/9; 95% CI, 21.2–86.3) and 88.9% (8/9; 95% CI, 51.8–99.7) at 6.0 mg/kg, respectively, and 36.7% (11/30; 95% CI, 19.9–56.1) and 86.7% (26/30; 95% CI, 69.3–96.2) at 8.0 mg/kg, respectively.

Conclusions

SHR-A1904 showed a manageable safety profile and promising anti-tumor activity in pretreated pts with CLDN18.2+ GC/GEJC.

Clinical trial identification

NCT04877717; Release date: May 7, 2021.

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

S. Wang, Q. Wu, J. Xie: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals. All other authors have declared no conflicts of interest.