Akeso Inc. has announced the enrollment of the first patient in a registrational Phase III clinical study evaluating Cadonilimab, a PD-1/CTLA-4 bispecific antibody, combined with chemotherapy versus Tislelizumab combined with chemotherapy for first-line treatment of patients with PD-L1 negative non-small cell lung cancer (NSCLC). The trial (NCT05990127) specifically targets patients with PD-L1 tumor proportion score (TPS) less than 1%.
Addressing a Critical Treatment Gap
The study addresses a substantial unmet medical need in lung cancer treatment. Retrospective studies conducted worldwide and in China have revealed that PD-L1 negative expression is observed in up to 48% of patients with driver gene-negative NSCLC. While immunotherapy combined with chemotherapy represents the first-line standard treatment for these patients, current treatment approaches provide limited survival benefits for the PD-L1 negative population.
According to Akeso, there exists a pressing clinical imperative for novel treatment modalities to enhance clinical outcomes for this patient population. The company notes that compared to PD-1/PD-L1 monoclonal antibodies, PD-1 monoclonal antibody plus CTLA-4 monoclonal antibody combined with chemotherapy provides greater benefits for the PD-L1 negative population.
Cadonilimab's Clinical Profile
Previous studies have demonstrated that Cadonilimab possesses a "high efficacy, low toxicity" profile and shows clinical efficacy in NSCLC patients with PD-L1 negative expression. The bispecific antibody has shown promising results across multiple cancer types, with clinical studies demonstrating that combination therapy with Cadonilimab as first-line treatment for advanced gastric cancer and advanced cervical cancer provides significant survival benefits for all-comer patients, irrespective of their PD-L1 expression levels.
The therapeutic approach exhibits robust anti-tumor effects even in patients with low PD-L1 expression or negative status, effectively addressing the limitations of current PD-1/PD-L1 monoclonal antibody immunotherapy. This mechanism has the potential to reshape the landscape of cancer treatment, according to the company.
Future Implications
Akeso anticipates that Cadonilimab, in the treatment of PD-L1 negative NSCLC population, will continue its unique advantages observed in gastric and cervical cancers. The company expects the therapy to become a new generation of efficient immunotherapy regimen for first-line treatment of advanced PD-L1 negative NSCLC patients.
The Phase III trial represents a critical step in potentially expanding treatment options for a significant subset of NSCLC patients who currently have limited therapeutic alternatives with meaningful survival benefits.
