Dr. Jiafu Ji, Dr. Ziyu Li, and Dr.  Lin Shen from Peking Cancer Hospital have co-authored a research paper titled “Cadonilimab with chemotherapy in HER2-negative gastric or gastroesophageal junction adenocarcinoma: the phase 1b/2 COMPASSION-04 trial”, published online in Nature Medicine. The study addresses several critical clinical issues, such as the limited benefit of PD-1 monoclonal antibody treatment, the high incidence of adverse effects with PD-1 and CTLA-4 combination therapy, and the ineffectiveness of PD-1 combined with chemotherapy in patients with low or negative CPS scores. To tackle these challenges, the researchers innovatively employed a domestically developed PD-1/CTLA-4 dual-target antibody in the COMPASSION-04 study, marking the first clinical trial globally to evaluate this combination as a first-line treatment for advanced gastric cancer.

The primary endpoints of the COMPASSION-04 study were: for the Phase Ib trial, the recommended Phase II dose (RP2D), and for the Phase II trial, the objective response rate (ORR). Both primary endpoints were successfully met.

At the 2023 American Society of Clinical Oncology (ASCO) annual meeting, 24-month follow-up survival data from the COMPASSION-04 study was presented for the first time. The follow-up duration in this publication extends to a median of 29.2 months. A total of 98 patients were enrolled in the study, receiving various doses of the PD-1/CTLA-4 dual-target antibody in combination with oxaliplatin plus capecitabine (XELOX) or modified XELOX (mXELOX).

• In Phase Ib, the RP2D was determined to be 6 mg/kg Q2W, with no dose-limiting toxicity observed. The combination of the PD-1/CTLA-4 dual-target antibody and chemotherapy demonstrated encouraging safety and antitumor response.
• In the Phase II trial, the PD-1/CTLA-4 dual-target antibody combined with chemotherapy as first-line treatment for advanced gastric/gastroesophageal junction adenocarcinoma showed significant clinical potential.

Key findings include:

• The objective response rate (ORR) was 52.1%, consisting of 4.3% complete response (CR) and 47.9% partial response (PR). The median duration of response (mDOR) was 13.73 months, and the median progression-free survival (PFS) was 8.18 months.
• Regardless of PD-L1 expression, the median overall survival (mOS) was 17.48 months, with a 12-month OS rate of 61.8%. For patients with a PD-L1 CPS score ≥ 5, the mOS was 20.32 months; for those with a CPS < 1, the mOS was 17.64 months.
• The combination therapy showed good tolerance, with no new safety concerns compared to PD-1 monotherapy. Common Grade ≥ 3 adverse events included decreased neutrophil count, platelet count, anemia, and white blood cell count.
• Notably, the interim analysis of the Phase III COMPASSION-15 clinical trial, presented by Professor Jiafu Ji at the 2024 American Association for Cancer Research (AACR) meeting, further confirmed the efficacy of this treatment.

In conclusion, clinical evidence supports that the PD-1/CTLA-4 dual-target antibody combined with chemotherapy can significantly improve overall survival and reduce the risk of death in patients with advanced gastric cancer, regardless of PD-L1 expression (high/low or negative). This combination therapy addresses the current limitations of PD-1 monotherapy in patients with low or negative PD-L1 CPS scores, filling a critical clinical gap and potentially rewriting treatment guidelines for gastric cancer.

This groundbreaking treatment for advanced gastric cancer is a testament to the expertise of Chinese researchers. These results, frequently featured at international medical conferences and in prestigious journals, highlight the strong combination of “Chinese scholars + Chinese innovative drugs.” The international academic community recognizes the strength of this dual-target immunotherapy, showcasing the leading role of Chinese researchers in clinical studies of cancer immunotherapy.