Dr Xu on the Preliminary Efficacy of SHR-A1904 in Gastric/GEJ Cancer

Ruihua Xu, MD, PhD, professor, medical oncology, Department of Medical Oncology, president, Sun Yat-sen University Cancer Center, chairman, Chinese Society of Clinical Oncology, discusses preliminary findings from the gastric/gastroesophageal junction (GEJ) cancer portion of a phase 1 trial (NCT04877717) investigating the Claudin 18.2 (CLDN18.2)–targeted antibody-drug conjugate SHR-A1904 in patients with advanced solid tumors.

This multicenter, open-label, 3-part, first-in-human trial is evaluating the safety and efficacy of SHR-A1904 in patients with pathologically confirmed, advanced solid tumors who have progressed on available standard therapies and have CLDN18.2-positive disease, an ECOG performance status of 0 or 1, and at least 1 measurable lesion per RECIST 1.1 criteria. In the dose-escalation phase, patients received SHR-A1904 every 3 weeks at doses ranging from 0.6 mg/kg to 8.0 mg/kg. The dose levels of 6.0 mg/kg and 8.0 mg/kg were selected for the pharmacokinetic- and efficacy-expansion portions of the trial.

At a data cutoff date of March 18, 2024, efficacy-evaluable patients in the gastric/GEJ cancer cohort who received the agent at 6.0 mg/kg (n = 9) achieved an overall response rate (ORR) of 55.6% (95% CI, 21.2%-86.3%). The disease control rate (DCR) in this patient population was 88.9% (95% CI, 51.8%-99.7%). Among efficacy-evaluable patients who received the agent at 8.0 mg/kg (n = 30), the ORR was 36.7% (95% CI, 19.9%-56.1%), and the DCR was 86.7% (95% CI, 69.3%-96.2%). In the total population (n = 58), the ORR was 27.6% (95% CI, 16.7%-40.9%), and the DCR was 81.0% (95% CI, 68.6%-90.1%).

These response rates may be the highest that have been achieved so far in this difficult-to-treat patient population, Xu says.

Among safety-evaluable patients who received the agent at 6.0 mg/kg (n = 15), any treatment-related adverse effects (TRAEs) occurred in 86.7%, and grade 3 or higher TRAEs occurred in 26.7%. Any TRAEs occurred in 94.7% of safety-evaluable patients who received the agent at 8.0 mg/kg (n = 38) and grade 3 or higher TRAEs occurred in 71.1%.

Disclosures: Dr Xu reports advisory board participation with Astellas, Merck Sharp and Dohme, AstraZeneca, Junshi, Hengrui, BeiGene, Innovent, CPPC, and Keymed Bioscience.