Akeso Launches Global Phase III Trial of Cadonilimab in First-Line HER2-Negative Gastric Cancer

Akeso has enrolled the first patient in COMPASSION-37, a global Phase III head-to-head trial evaluating cadonilimab plus chemotherapy against chemotherapy with or without nivolumab as first-line treatment for patients with previously untreated, unresectable or metastatic HER2-negative gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. The study will test whether dual PD-1 and CTLA-4 blockade can improve outcomes across diverse patient populations, including those with lower PD-L1 expression.

Global Phase III Trial Targets a Key Immunotherapy Question

COMPASSION-37 is being conducted across multiple international centers and is co-led by gastrointestinal oncology specialists from Memorial Sloan Kettering Cancer Center, Johannes Gutenberg University Mainz, and Peking University Cancer Hospital. Several investigators previously contributed to CheckMate 649; the Phase III study that established nivolumab plus chemotherapy as an important first-line treatment strategy for advanced HER2-negative gastric and related cancers.

The trial addresses a persistent clinical challenge: immunotherapy benefit in advanced gastric cancer varies with PD-L1 expression. Although PD-1 inhibitor combinations have become central to first-line treatment, patients with low PD-L1 expression generally derive less pronounced benefit. The source notes that treatment recommendations and PD-L1 thresholds also vary across regions, underscoring the need for broader evidence across patient populations.

Cadonilimab Combines PD-1 and CTLA-4 Blockade

Cadonilimab is a bispecific antibody that simultaneously targets PD-1 and CTLA-4, two immune checkpoint pathways that regulate antitumor T-cell activity. The development strategy is based on the potential for combined checkpoint blockade to generate broader immune activation than targeting either pathway alone.

The approach builds on results from COMPASSION-15 (NCT05008783), a randomized, double-blind, placebo-controlled Phase III trial involving 610 patients with HER2-negative advanced gastric or G/GEJ adenocarcinoma. Nearly half of enrolled patients had low PD-L1 expression, while 23% had PD-L1-negative disease. According to the source, cadonilimab plus chemotherapy significantly reduced the risk of death in the overall population compared with the control group, with benefit reported regardless of PD-L1 expression status.

COMPASSION-37 Moves Evidence into Global Validation

COMPASSION-37 will now test these findings against contemporary international treatment standards in a head-to-head Phase III setting. The central clinical question is whether dual PD-1/CTLA-4 blockade can extend meaningful immunotherapy benefit to patients who have historically obtained less benefit from PD-1 inhibitor-based therapy, particularly those with low PD-L1 expression.

Akeso also highlighted a U.S. Phase II perioperative study (NCT07631000), evaluating cadonilimab with FLOT chemotherapy in patients with locally advanced, resectable gastric or G/GEJ adenocarcinoma. The study is led by Yelena Janjigian at Memorial Sloan Kettering Cancer Center and is exploring the approach in earlier-stage disease.

Regulatory and Development Pathway Expands

Cadonilimab received its initial approval in China in June 2022 for relapsed or metastatic cervical cancer after platinum-based chemotherapy. China subsequently approved cadonilimab with fluoropyrimidine- and platinum-based chemotherapy for first-line locally advanced unresectable or metastatic gastric or G/GEJ adenocarcinoma in September 2024, followed by an additional cervical cancer approval in May 2025.

COMPASSION-37 represents the next major test of the program, moving evidence from Chinese Phase III development into a global, multicenter comparison with established first-line treatment strategies. Its results will determine whether the cadonilimab combination can demonstrate a clinically meaningful advantage across broader geographic populations and PD-L1 subgroups.

 Reference

First Patient Enrolled in Global Phase III Trial of Cadonilimab Versus Nivolumab in First-Line Gastric Cancer, Akeso, 28 September 2026