LBA60 - Phase III study of SHR-1701 versus placebo in combination with chemo as first-line (1L) therapy for HER2-negative gastric/gastroesophageal junction adenocarcinoma (G/GEJA)

Background

SHR-1701 is a bifunctional agent composed of an IgG4 mAb targeting PD-L1 fused with extracellular domain of the TGF-βIIR. We aimed to assess the addition of SHR-1701 to standard chemo in patients (pts) with previously untreated, unresectable locally advanced or metastatic HER2-negative G/GEJA.

Methods

This was a 2-part phase 3 study. In part 1, the recommended dose of SHR-1701 was determined to be 30 mg/kg, when combined with CAPOX. In the multicenter, randomized, double-blind, part 2, pts were randomized (1:1) to receive SHR-1701 (30 mg/kg, iv, q3w) or matching placebo, plus CAPOX. Randomization was stratified by PD-L1 CPS (≥5 vs <5), ECOG PS (0 vs 1), and peritoneal metastasis (yes vs no). Primary endpoint was OS, assessed in population with PD-L1 CPS ≥5 and in ITT population.

Results

From Mar 11, 2022 to Jan 13, 2024, 731 pts were randomly assigned to SHR-1701+chemo (N=365) or placebo+chemo (N=366). As of May 20, 2024, median follow-up was 8.5 mo (IQR 5.6–13.2). In pts with PD-L1 CPS ≥5, median OS was significantly prolonged with SHR-1701+chemo versus placebo+chemo (16.8 vs 10.4 mo; HR, 0.53 [95% CI 0.40–0.68]; p<0.0001). In ITT population, median OS was significantly improved with SHR-1701+chemo over placebo+chemo (15.8 vs 11.2 mo; HR, 0.66 [95% CI 0.53–0.81]; p<0.0001). PFS, ORR, and DoR with SHR-1701+chemo were also superior to placebo+chemo (Table). Grade ≥3 TRAEs were comparable between the two arms (62.6% vs 59.0%), with the most common being decreased platelet count (19.0% vs 28.1%), decreased neutrophil count (12.1% vs 16.4%), and anemia (19.8% vs 12.6%). Table: LBA60

Efficacy summary

*assessed per BICR.

Conclusions

1L SHR-1701 plus CAPOX showed a statistically significant and clinically meaningful benefit in OS compared with placebo plus CAPOX in pts with HER2-negative G/GEJA, both in PD-L1 CPS ≥5 population and in overall population regardless of PD-L1 level, presenting as a new treatment option.

Clinical trial identification

NCT04950322, Release date: July 6, 2021.

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

Z. Wang, W. Wang, H. Han: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals. All other authors have declared no conflicts of interest.