Akeso has announced that the first patient has been dosed in its global, multicentre, randomised Phase-II registrational trial (COMPASSION-36/AK104-225). The trial will evaluate Cadonilimab, Akeso's first-in-class PD-1/CTLA-4 bispecific antibody, in combination with Lenvatinib versus Lenvatinib alone for the treatment of advanced HepatoCellular Carcinoma (HCC) in patients previously treated with Atezolizumab (a PD-L1 inhibitor) and Bevacizumab.

COMPASSION-36 is the first global registrational Phase-III trial of Cadonilimab, currently ongoing in China, the US and Europe. Its advancement represents a significant milestone in the global development and registration of Cadonilimab, reflecting Akeso's commitment to advance cancer immunotherapy and address the limited survival benefits associated with single-target therapies.

Additional global multicentre registrational/Phase-III clinical trials for Cadonilimab are currently being prepared. Going forward, Akeso will continue to pursue a dual strategy of in-house development and open collaboration, leveraging high-quality global resources to accelerate the internationalisation of Cadonilimab and offer patients worldwide improved and more accessible treatment options.

Currently, immune checkpoint inhibitor (IO) combination therapies have become the standard first-line treatment for various advanced malignancies. However, for patients worldwide whose disease progresses after IO combination therapy, there is a lack of effective second-line treatment options. The very limited second-line treatment options for advanced malignancies drive the critical need to explore new therapeutic strategies. Cadonilimab-based combination therapies have shown substantial potential in overcoming IO resistance across multiple tumor types.

HCC is one of the most prevalent malignancies worldwide, with approximately 865,000 new cases of liver cancer reported globally in 2022. The combination of Atezolizumab and Bevacizumab (A+T regimen) is the standard first-line therapy for advanced HCC, as recommended by the NCCN guidelines. However, for patients whose disease progresses after first-line A+T treatment, there is currently no FDA-approved second-line therapy available in the US, and also no approved treatment options from the NMPA in China. This creates a significant unmet need in the clinical management of these patients.

The potential of Cadonilimab for the treatment of HCC has been validated in multiple studies. The promising data from the combination of Cadonilimab and Pulocimab (anti-VEGFR-2) in treating IO-resistant lung cancer was recently presented as an oral presentation at WCLC 2025, generating widespread attention within the industry. At the 2023 ESMO Asia Congress, a study was presented demonstrating that Cadonilimab, combined with FOLFOX-HAIC as neoadjuvant therapy, achieved a 100 percent Disease Control Rate (DCR) in patients with resectable multi-nodular HCC. Data presented at the 2023 ESMO Congress revealed that the combination of Cadonilimab and Lenvatinib as first-line treatment for advanced HCC shows superior anti-tumor activity.

Akeso's exploration of combination therapies with Cadonilimab in the treatment of HCC offers a broad and effective approach to disease management. These combinations address both early and advanced stages of HCC and provide promising therapeutic options for a wide range of patients.

In addition to the international multi-centre Phase-II registrational study COMPASSION-36, patient enrollment for the Phase-III clinical trial of Cadonilimab as adjuvant therapy for high-risk recurrence following curative surgery for HCC has been completed. Furthermore, a Phase-III registrational study of Cadonilimab combined with Lenvatinib and transarterial chemoembolisation (TACE) for the treatment of intermediate to advanced unresectable HCC is currently ongoing.