Novel SHR-1701 Combination Therapy Shows Promise in Reducing Chemotherapy-Induced Myelosuppression for Gastric Cancer Patients

A groundbreaking phase 3 clinical trial has revealed promising results for patients battling advanced gastric and gastroesophageal junction (GEJ) cancer, demonstrating that the novel bifunctional agent SHR-1701, when combined with standard chemotherapy, significantly reduces chemotherapy-induced myelosuppression.

The multicenter study, presented at the 2025 ASCO Gastrointestinal Cancer Symposium, evaluated the combination of SHR-1701, a dual-targeting PD-L1 and TGF-β agent, with CAPOX chemotherapy (capecitabine and oxaliplatin) against placebo plus CAPOX in patients with HER2-negative gastric or GEJ adenocarcinoma.

Improved Treatment Tolerance and Reduced Side Effects

The trial showed notable improvements in treatment tolerability, with patients receiving SHR-1701 experiencing fewer chemotherapy delays and dose reductions. The median treatment exposure for SHR-1701 plus CAPOX reached 137 days, compared to 127.5 days in the placebo group, suggesting better treatment sustainability.

Dr. Zhi Peng, associate professor at Beijing Cancer Hospital and principal investigator of the study, emphasized the significance of these findings: "SHR-1701 showed the capacity to suppress chemo-associated myelosuppression, as evidenced by fewer chemo delays and dose reductions; lower frequency of any grade, grade 3 [severe] or higher, and serious treatment-related hematological toxicities."

Key Hematological Outcomes

The study demonstrated significant reductions in hematological adverse events:

• Platelet count decreases: 59.6% in the SHR-1701 group vs. 68.3% in the placebo group (any grade)
• Neutrophil count decreases: 44.8% vs. 54.9% (any grade)
• White blood cell count decreases: 40.4% vs. 51.6% (any grade)

Severe (grade 3 or higher) adverse events were also notably lower in the SHR-1701 group across all hematological parameters.

Study Design and Patient Population

The trial enrolled 730 patients who were randomized to receive either 30 mg/kg of intravenous SHR-1701 (364 patients) or placebo (366 patients) in combination with CAPOX chemotherapy every three weeks. Eligible participants were adults with HER2-negative, unresectable locally advanced or metastatic gastric or GEJ adenocarcinoma who had not received prior systemic treatment.

Treatment Sustainability and Safety Profile

The combination therapy demonstrated favorable treatment sustainability with median relative dose intensities of 94.5%, 83.4%, and 91.1% for SHR-1701, capecitabine, and oxaliplatin, respectively. While treatment-related adverse events were common in both groups (97.8% vs. 98.4%), the SHR-1701 combination showed manageable safety profiles.

Clinical Implications

These findings represent a significant advancement in the management of chemotherapy-induced myelosuppression, a common challenge in cancer treatment. The ability to maintain higher dose intensities while reducing hematological complications could potentially lead to better treatment outcomes for patients with advanced gastric and GEJ cancers.

The study has already met its primary endpoint of superior overall survival for SHR-1701 plus CAPOX versus placebo plus CAPOX, particularly in patients with a PD-L1 combined positive score of 5 or more, suggesting a promising new treatment option for this patient population.