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HER2/EGFR in Cancer Research / Gastric Cancer Management and Outcomes · Journal article
Nature Communications · August 15, 2026
Encouraging direction, but not yet definitive.
A Phase Ib/II single-arm trial of sintilimab plus bevacizumab biosimilar IBI305 and CapeOX chemotherapy achieved the primary ORR endpoint of 87.0% in 54 patients with HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma, with median PFS of 12.2 months and manageable grade ≥3 toxicity in 66%. The lack of a randomized control arm and modest sample size limit the strength of evidence; confirmation in larger RCTs is necessary before conclusions about superiority or standard-of-care positioning.
Single-arm, Phase Ib/II trial. HER2-negative patients with advanced gastric or gastroesophageal junction adenocarcinoma, including subgroups stratified by PD-L1 CPS, Claudin-18.2 expression, and peritoneal metastasis status.. Intervention: Sintilimab (anti-PD-1 monoclonal antibody) plus IBI305 (bevacizumab biosimilar, anti-VEGF) plus CapeOX chemotherapy (capecitabine and oxaliplatin).. n = 54. Not specified in source text..
Phase Ib: no dose-limiting toxicities observed (N=9) Phase II ORR 87.0% (95% CI: 75.1–94.6%) in efficacy-evaluable population (N=54), achieving pre-specified target DCR 98.1% (95% CI: 90.1–100.0%)
Phase Ib: no dose-limiting toxicities observed (N=9) Grade ≥3 treatment-related adverse events in 66% of patients; most common: neutropenia (14%), fatigue (13%), thrombocytopenia (11%)
The high ORR and disease control rate are encouraging for this triple-agent combination, but clinicians should await randomized evidence before adoption. The manageable toxicity profile and benefit across biomarker subgroups suggest potential broad applicability, pending confirmation.
Single-arm Phase II trial with a clear efficacy endpoint (ORR 87.0%) and manageable safety profile, but lacks a randomized comparator and modest sample size, necessitating confirmation in larger RCTs.
As stated by the source record.
Quoted from the source exactly as published.
The high ORR and disease control rate are encouraging for this triple-agent combination, but clinicians should await randomized evidence before adoption. The manageable toxicity profile and benefit across biomarker subgroups suggest potential broad applicability, pending confirmation.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Adding anti-PD-1 or anti-VEGF therapy to chemotherapy improves survival in patients with advanced gastric cancer, yet outcomes remain poor. This Phase Ib/II trial aimed to evaluate the efficacy and safety of combining sintilimab, the bevacizumab biosimilar IBI305, and CapeOX chemotherapy as a first-line treatment for patients with HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma (GA/GEJA). In phase Ib, no dose-limiting toxicities (DLTs) that served as the primary endpoint were observed (N = 9). In phase II, the primary endpoint of the objective response rate (ORR) in the efficacy-evaluable population (N = 54) was 87.0% (95% CI: 75.1–94.6%), achieving the pre-specified target was reached. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), and safety. The DCR was 98.1% (95% CI: 90.1–100.0%). At a median follow-up of 20.3 months, median PFS and DoR were 12.2 months (95% CI: 9.2–18.1) and 12.5 months (95% CI: 9.4–NE), respectively, while the median OS was not reached. A clinical benefit was observed regardless of PD-L1 CPS, Claudin-18.2 expression status, or the presence of peritoneal metastases. Treatment-related adverse events of grade ≥3 occurred in 66% of patients; the most common were neutropenia (14%), fatigue (13%), and thrombocytopenia (11%). The limitations of the study include the single-arm, non-randomized design and the modest sample size, which necessitate confirmation in larger randomized controlled trials. Nonetheless, sintilimab plus IBI305 and chemotherapy demonstrated promising antitumor activity and favorable PFS with manageable toxicity in HER2-negative advanced GA/GEJA. Trial number: NCT05640609. Previous evaluations on anti-VEGF monoclonal antibody indicate its therapeutic potential in gastric cancer treatment. Here this group reports a phase Ib/II trial combining sintilimab/bevacizumab biosimilar IBI305/CapeOX chemotherapy as the first-line treatment on 54 patients with HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma.
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