AACR 2024: Positive Phase III Results for Cadonilimab Combo in Advanced Gastric Cancer

A recent breakthrough in the treatment of advanced gastric cancer has been reported by Akeso, Inc., with the presentation of their Phase III clinical study results at the 2024 AACR conference. The study, known as COMPASSION-15, is pioneering in its approach, being the first to combine a PD-1/CTLA-4 bispecific antibody, Cadonilimab, with chemotherapy as a first-line treatment for this type of cancer.
The study's patient population included a significant number of individuals with low or negative PD-L1 expression, typically known to respond poorly to immunotherapy. However, the interim analysis revealed promising results. With a median follow-up period of 18.7 months, the Cadonilimab combination therapy demonstrated a significant improvement in overall survival and a reduced risk of death compared to chemotherapy alone. This was observed across all PD-L1 expression levels, including patients with low PD-L1 expression, suggesting that the combination therapy could potentially overcome the limitations of PD-1 monotherapy.
The study's findings were particularly noteworthy in the intention-to-treat (ITT) population, where the median overall survival was longer for the combination therapy group (15.0 months) than for the chemotherapy group (10.8 months), translating to a 39% prolongation of median overall survival and a 38% reduction in the risk of death. The benefits were consistent across different PD-L1 expression levels, with the combination therapy showing a median progression-free survival of 7.0 months, compared to 5.3 months for chemotherapy, indicating a 32% prolongation and a 47% reduction in the risk of disease progression.
The efficacy of Cadonilimab in anti-tumor response was also highlighted, with the combination therapy doubling the duration of response compared to chemotherapy. The objective response rate was 65.2% for the combination therapy, a 33.3% increase over the chemotherapy rate of 48.9%. Moreover, the median duration of response was significantly longer at 8.8 months for the combination therapy, as opposed to 4.4 months for chemotherapy.
Long-term survival was significantly enhanced with Cadonilimab combination therapy, with the 12-month and 18-month overall survival rates showing a clear advantage for the combination therapy across all CPS levels. The 12-month overall survival rates were 57.3% for the combination therapy and 43.7% for chemotherapy, while the 18-month rates were 45.8% and 25.5%, respectively.
The success of the AK104-302/COMPASSION-15 study has led to the acceptance of Akeso's new drug application for Cadonilimab in combination with XELOX for the first-line treatment of unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, offering a new hope for patients with advanced gastric cancer.