The COMPASSION-15 trial (NCT05008783), a Phase III study evaluating Cado, a PD-1/CTLA-4 bispecific antibody, in combination with chemotherapy, was presented by Prof. Lin Shen at the ESMO Congress 2025. The trial investigated the efficacy and safety of Cado plus chemotherapy compared with chemotherapy alone as first-line treatment for patients with HER2-negative advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. These final data confirm and expand upon the previously reported interim results, demonstrating sustained overall survival (OS) and progression-free survival (PFS) benefits across PD-L1 subgroups with a manageable safety profile.
Background
Despite progress in systemic therapies for advanced gastric and gastroesophageal junction cancers, long-term survival remains limited, particularly among HER2-negative patients. Immunotherapy combinations have reshaped treatment paradigms, yet resistance and variable PD-L1 expression continue to challenge durable disease control. Cado, a novel PD-1/CTLA-4 bispecific antibody, was designed to provide deeper and more sustained immune activation than single-checkpoint blockade.
Methods of COMPASSION-15 Trial
A total of 610 patients with previously untreated, HER2-negative, unresectable, locally advanced, or metastatic G/GEJ adenocarcinoma were randomized 1:1 to receive Cado (10 mg/kg every 3 weeks) plus chemotherapy (XELOX) or placebo plus chemotherapy. The primary endpoint was overall survival in the intention-to-treat population. The data cutoff for the final analysis was December 6, 2024.
Results of COMPASSION-15 Trial (Cado+Chemo vs Chemo)
After a median follow-up of 33.9 months, Cado + chemo continued to show significant improvement in both OS and PFS compared with chemotherapy alone, regardless of PD-L1 expression.
- Overall Survival (All randomized): 13.9 mo vs 11.1 mo (HR 0.61; 95% CI 0.51–0.73; p < 0.001)
- Progression-Free Survival (All randomized): 7.0 mo vs 5.3 mo (HR 0.51; 95% CI 0.42–0.62; p < 0.001)
- In patients with PD-L1 CPS ≥ 5, median OS was 16.8 months with Cado + chemo vs 10.8 months with chemo alone (HR 0.49; p < 0.001).
- In patients with PD-L1 CPS <5, median OS was 13.2 months with Cado + chemo vs 11.3 months with chemo alone (HR 0.76; p < 0.019).
- Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 66.9% of patients in the Cado arm and 53.6% in the control arm. Treatment-related deaths occurred in 2.0% and 2.6%, respectively. No new or unexpected safety signals were observed.
Conclusions
With an additional 16 months of follow-up, Cado + chemotherapy maintained durable and clinically meaningful survival benefits compared with chemotherapy alone, independent of PD-L1 status. These findings further support Cado + chemo as a potential new standard of care for the first-line treatment of HER2-negative advanced G/GEJ adenocarcinoma.
You can read the full abstract here