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Cancer Cells and Metastasis / HER2/EGFR in Cancer Research / Gastric Cancer Management and Outcomes · Journal article
Cancer Discovery · August 14, 2026
Encouraging direction, but not yet definitive.
This single-arm phase II trial demonstrates that a first-line triplet regimen of disitamab vedotin (HER2-targeting ADC), tislelizumab (anti-PD-1), and S-1 chemotherapy achieves a 89.5% confirmed objective response rate and median PFS of 13.8 months in HER2-overexpressing advanced gastric and gastroesophageal junction adenocarcinoma. The absence of a control arm means efficacy cannot be compared directly to standard care, and the results are preliminary evidence supporting further evaluation in a randomized setting.
Single-arm, multicenter phase II trial. Patients with unresectable or metastatic HER2-overexpressing gastric or gastroesophageal junction adenocarcinoma, no prior systemic therapy.. Intervention: Triplet combination: disitamab vedotin 2.5 mg/kg IV on day 1 of 21-day cycle, tislelizumab 200 mg IV on day 1 of each cycle, and oral S-1 40–60 mg twice daily.. n = 57. Multicenter (specific sites and countries not stated in source)..
Confirmed objective response rate of 89.5% (n=51/57), including 5 complete responses Median progression-free survival of 13.8 months Median overall survival of 31.9 months
Safety profile shows 100% adverse event rate; long-term tolerability and quality of life not fully characterized in this abstract. All 57 patients experienced an adverse event; 26.3% (n=15/57) with serious adverse events and 19.3% (n=11/57) with treatment-related serious adverse events
If confirmed in a randomized trial, these results suggest a potential new first-line standard for HER2-overexpressing advanced gastric cancer. Clinicians should await phase III data before adopting this regimen outside of clinical trials, given the single-arm design and lack of direct comparison to existing first-line options.
Single-arm phase II trial with clear efficacy signals (89.5% ORR, 13.8-month PFS) in a treatment-naïve population, but lacks a comparator and represents early-stage evidence requiring confirmation in a randomized trial.
As stated by the source record.
Quoted from the source exactly as published.
If confirmed in a randomized trial, these results suggest a potential new first-line standard for HER2-overexpressing advanced gastric cancer. Clinicians should await phase III data before adopting this regimen outside of clinical trials, given the single-arm design and lack of direct comparison to existing first-line options.
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.
HER2 is overexpressed in a subset of gastric and gastroesophageal junction (G/GEJ) adenocarcinomas, representing a therapeutic vulnerability that may be targeted by a number of approved or emerging HER2-specific modalities. Disitamab vedotin is a HER2-targeting antibody–drug conjugate (ADC) connected via a cleavable linker to monomethyl auristatin E, a cytotoxic payload. The first domestically developed ADC to be approved in China, disitamab vedotin is approved for the treatment of G/GEJ adenocarcinoma with HER2 overexpression in the third-line setting after patients have received two rounds of chemotherapy. To explore whether HER2-targeting ADCs may provide benefit at earlier stages of disease, Li, Liu, and colleagues initiated a single-arm, multicenter phase II trial. Fifty-seven patients with unresectable or metastatic G/GEJ adenocarcinoma with HER2 overexpression received, as first-line therapy, a triplet combination of disitamab vedotin, the anti–PD-1 antibody tislelizumab, and oral S-1 chemotherapy. Disitamab vedotin and tislelizumab were administered intravenously on the first day of a 21-day cycle at 2.5 mg/kg and 200 mg, respectively, while oral S-1 was administered at 40–60 mg twice daily. The primary endpoint was confirmed objective response, as assessed by computed tomography or magnetic resonance imaging, and secondary endpoints included progression-free survival, overall survival, duration of response, and safety. The triplet combination achieved a confirmed objective response rate of 89.5% (n = 51/57), in which five patients exhibited a complete response. The combination led to a median progression-free survival of 13.8 months, overall survival of 31.9 months, and duration of response of 13.3 months. All 57 patients experienced an adverse event, including 26.3% (n = 15/57) with a serious adverse event and 19.3% (n = 11/57) with a treatment-related serious adverse event. Exploratory molecular analyses provided evidence that the triplet combination increased T-cell clonality on treatment compared with baseline in the subset of patients with progression-free survival of 12 months or longer, supporting expansion of an immune response. Overall, the results of this phase II trial support the safety and efficacy of first-line disitamab vedotin with tislelizumab and S-1 in the first-line treatment of patients with G/GEJ adenocarcinoma, suggesting that this regimen warrants further clinical evaluation.Li S, Liu Z, Liu Y, Li K, Cong L, Cao F, et al. First-Line Disitamab Vedotin, Tislelizumab, and S-1 in HER2-Overexpressing Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: A Single-Arm, Phase II Trial. J Clin Oncol 2026 Jun 26 [Epub ahead of print].Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at https://aacrjournals.org/cdnews.
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