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YANTAI, China, June 3, 2025 /PRNewswire/ — On June 2 (Chicago time), in an oral presentation at the 2025 ASCO Annual Meeting, Dr. Lin Shen from Beijing Cancer Hospital presented the results of a Phase 2 clinical study conducted in China evaluating the efficacy and safety of disitamab vedotin (DV), developed by Remegen Co., Ltd., and toripalimab (PD-1) combined with CAPOX or trastuzumab as the first-line therapy for HER2-expressing patients with locally advanced or metastatic (la/m) gastric cancer. Comparing to the control group who received standard-of-care therapy, the DV combination therapy demonstrated clinically meaningful efficacy improvement, potentially to benefit patients who are non-responders to traditional targeted therapies.
The data presented are from the Phase 2 part of a randomized, multi-cohort, seamlessly connecting Phase 2/3 study, which enrolled systematic chemotherapy-native patients with different HER2 expression levels. As of April 7, 2025, the results showed:
- Among HER2-overexpressing gastric cancer patients, compared to the PD-1-trastuzumab-CAPOX combination therapy, DV and PD-1 + chemotherapy as well as DV and PD-1 + trastuzumab both demonstrated statistically significant efficacy and favorable safety profiles.
- Objective response rate (ORR): 66.7% vs 82.4% vs 68.8%;
- Median progression-free survival (mPFS): NR vs NR vs 14.1 months, with risk of disease progression decreasing by 54%（HR=0.46）and 41% (HR: 0.59);
- 12-month PFS rate: 66.3%, 67% and 53.6%；
- Common TRAEs of grade 3-5: diarrhea, neutrophil count decreased, platelet count decreased, etc.
- In patients with HER2-low-expressing gastric cancer, promising efficacy was observed with DV + PD-1 + CAPOX comparing to PD-1 + CAPOX, with a manageable safety profile.
- ORR: 72.0% vs 47.8%;
- mPFS: 9.9 vs 7.2 months, with risk of disease progression decreasing by 31% (HR: 0.69);
- Common TRAEs of grade 3-5: diarrhea, neutrophil count decreased, platelet count decreased, etc.
- Dose optimization conducted in patients with HER2-median/low-expressing gastric cancer. Compared to PD-1 + CAPOX, DV at 2.5 mg/kg or 2.0 mg/kg combined with PD-1 + reduced-dose CAPOX showed significant efficacy, and better safety over the full-dose chemotherapy.
- ORR: 71.4% vs 66.7% vs 56.3%;
- 6-month PFS rate: 71.4%，72.7% and 53.3%.
Globally, this is the first study to explore the triple combination therapy of “HER2 ADC + PD-1 + targeted medication” as first-line treatment of patients with la/m gastric cancer, pioneering a new mode of synergistic therapy. The multi-cohort design of this study provides precision treatment regimen for gastric cancer patients with different level of HER2 expression. For the HER2-overexpressing gastric cancer patients, DV + PD-1 + trastuzumab has the potential to become the new standard first-line treatment; for the HER2-low-expressing gastric cancer patients, DV + PD-1 + chemotherapy has the potential to fill the treatment gap of these patients. Based on the data obtained from the phase 2 study, the phase 3 clinical study of the triple combination therapy in patients with HER2-median/low-expressing gastric cancer has been initiated in April, 2025, in which 616 participants were planned to be enrolled, to further validate the efficacy of the DV combination therapy.
Gastric cancer is the fifth most common malignant tumor in the world, and China accounts for about 42.6% of new cases and 45.0% of deaths worldwide. HER2 is an important target in the treatment of gastric cancer, while the traditional targeted drug trastuzumab is only effective in the population with high expression (IHC 3+ or IHC 2+/FISH+), and can easily become resistant. There is a lack of effective targeted therapy options for patients with low/median HER2 expression (IHC 1+ or IHC 2+/FISH-), and the efficacy of chemotherapy combined with immunotherapy is not satisfactory.
As the first domestic HER2-targeted ADC drug in China, DV not only precisely kills tumor cells with HER2 over expression but also attacks adjacent cells with HER2 low expression through the bystander effect. Preclinical studies have also shown that the combination of DV with PD-1 inhibitor and trastuzumab can enhance anti-tumor activity.
