Dr Peng on the Efficacy of SHR-1701 Plus Chemotherapy in HER2– Gastric/GEJ Cancer

Zhi Peng, MD, associate professor, Beijing Cancer Hospital, Peking University, discusses findings from a phase 3 study (NCT04950322) of SHR-1701 vs placebo in combination with chemotherapy in the first-line treatment of patients with HER2-negative gastric/gastroesophageal junction (GEJ) adenocarcinoma.

SHR-1701 is a bifunctional agent that consists of an IgG4 monoclonal antibody targeting PD-L1 that is fused with the extracellular domain of the TGF-βIIR. This study evaluated the efficacy of adding SHR-1701 to standard chemotherapy in patients with previously untreated, unresectable, locally advanced or metastatic HER2-negative disease and was conducted in 2 parts. In part 1, the recommended dosage of SHR-1701 was established at 30 mg/kg in combination with CAPOX. Part 2 was a multicenter, randomized, double-blind study where patients were randomly assigned in a 1:1 ratio to receive chemotherapy plus either SHR-1701 at 30 mg/kg intravenously every 3 weeks or a matching placebo.

Notably, Peng and colleagues shared data from the investigation at the 2024 ESMO Congress. Between March 11, 2022, and January 13, 2024, a total of 731 patients were randomly assigned to receive either SHR-1701 plus chemotherapy (n = 365) or placebo plus chemotherapy (n = 366). As of May 20, 2024, the median follow-up duration was 8.5 months (interquartile range, 5.6-13.2). Among patients with a PD-L1 combined positive score of 5 or higher, the median overall survival (OS) was significantly longer in the SHR-1701 plus chemotherapy group compared with the placebo plus chemotherapy group at 16.8 months (95% CI, 14.7-not reached) vs 10.4 months (95% CI, 9.0-12.1 [HR, 0.53; 95% CI, 0.40-0.68; P < .0001]). In the intention-to-treat population, the median OS was also significantly higher with SHR-1701 plus chemotherapy vs placebo plus chemotherapy at 15.8 months (95% CI, 14.0-16.9) vs 11.2 months (95% CI, 9.4-12.1 [HR, 0.66; 95% CI, 0.53-0.81; P < .0001]). Additionally, progression-free survival, overall response rate, and duration of response outcomes with SHR-1701 plus chemotherapy were superior to those observed with the placebo plus chemotherapy regimen, Peng concludes.