Cadonilimab Plus Chemotherapy Demonstrates Sustained Survival Benefit in Advanced Gastric Cancer Final Analysis
Key Insights
The phase 3 COMPASSION-15 trial's final analysis confirms cadonilimab plus XELOX (search) chemotherapy significantly improved overall survival to 13.9 months versus 11.1 months with chemotherapy alone in first-line treatment of advanced gastric/GEJ adenocarcinoma.
Survival benefits were observed across all PD-L1 (search) expression levels, with particularly strong results in patients with PD-L1 CPS ≥5 showing 16.8 months median overall survival compared to 10.8 months with chemotherapy alone.
The bispecific PD-1 (search)/CTLA-4 (search) antibody maintained a manageable safety profile with no new long-term adverse effects identified after 33.9 months median follow-up.
The final analysis of the phase 3 COMPASSION-15 trial demonstrates that cadonilimab (AK104) plus XELOX (search) chemotherapy maintains clinically meaningful long-term survival benefits compared to chemotherapy alone as first-line treatment for patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma, regardless of PD-L1 (search) expression status.
Sustained Overall Survival Advantage
At a median follow-up of 33.9 months, the combination therapy achieved a median overall survival (OS) of 13.9 months (95% CI, 12.0-16.8) in the experimental arm versus 11.1 months (95% CI, 10.2-12.2) in the control arm, representing a 39% reduction in the risk of death (HR, 0.61; 95% CI, 0.51-0.73; P < .001).
"The efficacy and safety results in the final analysis demonstrated the long-term OS benefits of cadonilimab plus chemotherapy and will further strengthen its leading position as a standard of care in first-line treatment for [patients with] gastric/GEJ adenocarcinoma," stated Lin Shen, MD, lead study author and vice president of Clinical Oncology at Beijing Cancer Hospital (search) and Peking University (search).
The 12- and 24-month OS rates in the cadonilimab arm were 55.6% and 36.0%, respectively, compared to 44.9% and 14.8% in the placebo arm.
Progression-Free Survival and Response Duration
The median progression-free survival (PFS) was 7.0 months (95% CI, 6.7-8.4) with cadonilimab plus chemotherapy versus 5.3 months (95% CI, 4.5-5.6) with chemotherapy alone (HR, 0.51; 95% CI, 0.42-0.62; P < .001). The median duration of response was significantly extended to 8.9 months (95% CI, 7.0-11.1) in the experimental arm compared to 4.5 months (95% CI, 4.2-5.5) in the control arm (HR, 0.45; 95% CI, 0.35-0.59; P < .001).
Benefits Across PD-L1 Expression Levels
The survival advantage was consistent across all prespecified PD-L1 (search) combined positive score (CPS) cutoffs. In patients with PD-L1 CPS ≥5, the median OS reached 16.8 months (95% CI, 11.3-25.1) with cadonilimab versus 10.8 months (95% CI, 9.0-12.9) with placebo (HR, 0.49; 95% CI, 0.36-0.65; P < .001).
Even in patients with lower PD-L1 (search) expression (CPS <5), cadonilimab demonstrated benefit with a median OS of 13.2 months (95% CI, 11.2-15.6) compared to 11.3 months (95% CI, 10.1-13.0) with placebo (HR, 0.76; 95% CI, 0.59-0.99; P = .0019).
Trial Design and Patient Population
The COMPASSION-15 trial enrolled 610 patients with previously untreated, locally advanced, unresectable or metastatic, HER2-negative gastric/GEJ adenocarcinoma. Patients were randomized 1:1 to receive either 10 mg/kg of cadonilimab every 3 weeks plus XELOX (search) for a maximum of 6 cycles, followed by cadonilimab maintenance, or placebo plus XELOX followed by placebo maintenance.
The patient population was representative of clinical practice, with a median age of 63.7 years, predominantly male patients (78.4%), and most having metastatic disease (96.1%). PD-L1 (search) CPS expression varied across the population: 23.6% had CPS <1%, 27.9% had CPS 1-4%, 14.4% had CPS 5-9%, and 23.6% had CPS ≥10%.
Safety Profile Remains Manageable
Treatment-related adverse events (TRAEs) occurred in 99.0% of patients in the experimental arm versus 97.4% in the control arm, with grade ≥3 TRAEs occurring in 66.9% versus 53.6%, respectively. The most common grade 3 or greater TRAEs included decreased platelet count, decreased neutrophil count, anemia, decreased white blood cell count, and hypokalemia.
Serious TRAEs occurred in 40.0% of patients receiving cadonilimab compared to 26.0% in the control arm, while TRAEs leading to discontinuation occurred in 23.9% versus 6.6%, respectively. Treatment-related deaths occurred in 2.0% of the experimental arm and 2.6% of the control arm.
"No new long-term adverse effects were identified; the safety profile remained essentially consistent with that observed at the interim analysis," Shen concluded.
Regulatory Status and Clinical Impact
Cadonilimab is a humanized bispecific antibody targeting both PD-1 (search) and CTLA-4 (search) pathways. In September 2024, the National Medical Products Administration approved the agent for use in combination with fluoropyrimidine and platinum-based chemotherapy for first-line treatment of patients with locally advanced, unresectable or metastatic gastric/GEJ adenocarcinoma, based on interim findings from this trial.
These final results, with an additional 16 months of follow-up beyond the interim analysis, confirm the sustained clinical benefit of dual checkpoint inhibition in this challenging patient population where long-term survival remains limited despite therapeutic advances.