On August 4, 2025 Akeso, Inc. (9926.HK) ("Akeso" or the "Company") reported that its global, multicenter, randomized Phase II registrational trial (COMPASSION-36/AK104-225) has been approved to initiate by both China’s National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA) (Press release, Akeso Biopharma, AUG 4, 2025, View Source [SID1234654739]). 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. Akeso is now moving forward with the initiation of the study.

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The COMPASSION-36/AK104-225 study is a key part of cadonilimab’s global development for hepatocellular carcinoma, continuing Akeso’s mission to advance cancer immunotherapy standards and to address the current limited survival benefits of single-target therapies. This international, multicenter Phase II trial is designed to tackle the common issue of limited treatment options following resistance to immune checkpoint inhibitors (IO) in cancer therapy.

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 drives the critical need to explore new therapeutic strategies. Cadonilimab-based combination therapies have shown substantial potential in overcoming IO resistance across multiple tumor types.

Hepatocellular carcinoma (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 U.S., and also no approved treatment options from the NMPA in China. This creates a significant unmet need in the clinical management of these patients.

Cadonilimab is the first bispecific antibody for cancer immunotherapy to be approved globally and also the first bispecific antibody to be approved in China. The potential of cadonilimab for the treatment of HCC has been validated in multiple studies：

At the 2023 European Society for Medical Oncology Asia Congress (ESMO Asia), a study was presented demonstrating that cadonilimab, combined with FOLFOX-HAIC as neoadjuvant therapy, achieved a 100% disease control rate (DCR) in patients with resectable multinodular HCC, with an acceptable safety profile.
Additionally, data presented at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress revealed that the combination of cadonilimab and lenvatinib as first-line treatment for advanced HCC shows superior antitumor activity compared to currently approved therapies for advanced HCC.
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 multicenter 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 chemoembolization (TACE) for the treatment of intermediate to advanced unresectable HCC is currently ongoing.
Additionally, multiple Phase II studies investigating cadonilimab in combination with pulocimab (VEGFR-2), ivonescimab (PD-1/VEGF), and other therapies are currently underway for PD-1/L1 inhibitor-resistant non-small cell lung cancer (NSCLC), HCC, and other malignancies. These studies demonstrate cadonilimab’s potential in treating IO-resistant tumors.
Dr. Yu Xia, Founder, Chairwoman, President, and CEO of Akeso, remarked, "We are excited to initiate cadonilimab’s first international multicenter registrational trial, a pivotal step in addressing the global challenge of cancer immunotherapy resistance. This study represents a key milestone in Akeso’s global strategy to address the substantial clinical unmet needs in oncology. Akeso is advancing the clinical development of its innovative pipeline, including ivonescimab, cadonilimab, ligufalimab (CD47), and AK146D1 (Trop2/Nectin4 bispecific ADC) through both in-house initiatives and strategic global collaborations. Our goal is to provide accessible and impactful survival benefits to patients worldwide, and to position Akeso at the forefront of oncology innovation."