LBA53 - Sintilimab plus chemotherapy (chemo) versus chemo as first-line treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (ORIENT-16): First results of a randomized, double-blind, phase III study

Background

ORIENT-16 is a randomized, double-blind, phase 3 trial to evaluate the efficacy and safety of sintilimab in combination with chemo (S+C) vs chemo (C) as the first-line treatment for patients (pts) with advanced G/GEJ adenocarcinoma. We report the first results from a pre-specified interim analysis.

Methods

Eligible pts were adults (≥18 years) with untreated, unresectable locally advanced or metastatic G/GEJ adenocarcinoma, regardless of PD-L1 expression. Pts were randomized 1:1 to receive sintilimab (3mg/kg and 200 mg, respectively, for body weights <60kg and ≥60kg, IV Q3W) or placebo plus chemo (CapeOX: oxaliplatin 130 mg/m² IV Q3W, up to 6 cycles, capecitabine 1000 mg/m² PO Bid d1-14 Q3W) for up to 24 months. The primary endpoints were OS in the pts with CPS ≥5 and all randomized pts. Data cutoff date for interim analysis was June 20, 2021.

Results

As of the cutoff date, 650 pts were randomized (327 in S+C and 323 in C), including 397 (61.1%) pts with CPS≥5. Median follow-up was 18.8 months (range 0.0-29.1). S+C showed a significant improvement in OS vs C in pts with CPS≥5 (median 18.4 vs 12.9 mo; HR 0.660; 95%CI 0.505-0.864; P =0.0023) and all pts (median 15.2 vs 12.3 mo; HR 0.766; 95%CI 0.626-0.936; P =0.0090). OS benefits were consistently observed at all pre-specified CPS cutoffs (CPS ≥1, 5, and 10). PFS was superior with S+C vs C in pts with CPS≥5 (HR 0.628; 95%CI 0.489-0.805; P =0.0002) and all pts (HR 0.636; 95%CI 0.525-0.771; p<0.0001). Unconfirmed ORR were 72.8% vs 59.6% in pts with CPS≥5 and 65.1% vs 58.7% in all pts with measurable disease, with a median DOR of 8.4 vs 5.5 and 8.6 vs 5.5 months, respectively. Among all treated pts, 196 (59.8%) of 328 in S+C and 168 (52.5%) of 320 in C experienced grade ≥3 treatment-related adverse events (TRAEs). TRAE leading to death were occurred in 6 (1.8%) pts in S+C and 2 (0.6%) in C.

Conclusions

Sintilimab is the first PD-1 inhibitor that demonstrated superior OS and PFS with an acceptable safety profile, in combination with chemo, in Chinese pts with G/GEJ cancer regardless of PD-L1 expressions. Sintilimab plus chemo provides a new standard first-line treatment option for these pts.

Clinical trial identification

NCT03745170. First posted November 19, 2018.

Editorial acknowledgement

Legal entity responsible for the study

Innovent Biologics (Suzhou) Co., Ltd.

Funding

Innovent Biologics (Suzhou) Co., Ltd.

Disclosure

Y. Guo: Financial Interests, Personal, Full or part-time Employment: Innovent Biologics Co., Ltd. Z. Li: Financial Interests, Personal, Full or part-time Employment: Innovent Biologics Co., Ltd. Y. Liu: Financial Interests, Personal, Full or part-time Employment: Innovent Biologics Co., Ltd. Y. Wang: Financial Interests, Personal, Full or part-time Employment: Innovent Biologics Co., Ltd. H. Zhou: Financial Interests, Personal, Full or part-time Employment: Innovent Biologics Co., Ltd. All other authors have declared no conflicts of interest.