Akeso launches global Phase II trial of cadonilimab for IO-resistant liver cancer patients

What is the scope of Akeso’s latest global Phase II trial for cadonilimab in treatment-resistant liver cancer?

Akeso, Inc. (HKEX: 9926.HK) has officially dosed the first patient in its global multicenter Phase II registrational trial for cadonilimab, its pioneering PD-1/CTLA-4 bispecific antibody. This marks a critical milestone in the company’s expanding international immuno-oncology pipeline. The study, titled COMPASSION-36 (AK104-225), is a randomized trial evaluating cadonilimab in combination with lenvatinib, compared to lenvatinib alone, for the treatment of advanced hepatocellular carcinoma (HCC) in patients previously treated with the atezolizumab–bevacizumab combination—a standard first-line therapy.

Currently underway across China, the United States, and Europe, the COMPASSION-36 trial represents Akeso’s first global registrational Phase II/III trial for cadonilimab, positioning the drug candidate for broader international regulatory filings.

Akeso’s decision to advance cadonilimab in a post-immunotherapy setting reflects a growing consensus within the oncology community that new options are urgently needed for patients who progress after front-line immune checkpoint inhibitor (IO) regimens. With no currently approved second-line standard-of-care treatments for this patient group in either the U.S. or China, cadonilimab’s performance in this trial could play a pivotal role in reshaping clinical pathways in advanced liver cancer.

Why is cadonilimab positioned as a potential solution for IO-resistant advanced hepatocellular carcinoma?

Immunotherapy has become the cornerstone of first-line treatment for advanced HCC, with the combination of atezolizumab (PD-L1 inhibitor) and bevacizumab (anti-VEGF) widely accepted as the global gold standard. Yet, once patients experience disease progression on this regimen, therapeutic choices become sharply limited. As of September 2025, there are no FDA-approved or NMPA-approved second-line IO-based therapies that specifically address this unmet need.

Akeso is targeting this gap directly. The bispecific mechanism of cadonilimab—which engages both PD-1 and CTLA-4 pathways simultaneously—has demonstrated promise in overcoming resistance to prior IO therapies in multiple tumor types. In hepatocellular carcinoma, early data suggest that cadonilimab, particularly in combination settings, could provide a durable immunological reset even after prior checkpoint exposure.

Institutional sentiment surrounding bispecific antibodies has generally grown more favorable in recent years, as next-generation IO agents look to push past the ceiling of single-target therapies. Analysts note that the combination of PD-1 and CTLA-4 blockade in a single molecule could reduce toxicity compared to dual antibody regimens while maintaining or improving efficacy.

What previous clinical data supports cadonilimab’s expansion into global HCC treatment strategies?

Akeso has previously presented encouraging multi-tumor data on cadonilimab in various immunotherapy-resistant populations. Of particular relevance to HCC is the company’s ongoing research in both lung cancer and liver cancer cohorts where cadonilimab has been paired with VEGF inhibitors or chemotherapeutic backbones.

At the 2023 ESMO Asia Congress, a neoadjuvant study combining cadonilimab with FOLFOX-HAIC (hepatic arterial infusion chemotherapy) achieved a 100% disease control rate (DCR) in patients with resectable multinodular HCC, a setting historically associated with poor prognosis and high recurrence risk.

More recently, data presented at the 2023 ESMO Congress demonstrated the effectiveness of cadonilimab plus lenvatinib as a first-line regimen for advanced HCC, showing superior anti-tumor activity. That combination is now being formally tested in the COMPASSION-36 trial for post-IO progression.

Another compelling signal came from a separate lung cancer study, presented at WCLC 2025, where cadonilimab was combined with pulocimab (anti-VEGFR2) in IO-pretreated patients. The results were significant enough to garner oral presentation status, further validating cadonilimab’s potential across multiple tumor types where resistance mechanisms are increasingly a concern.

Taken together, these data have positioned cadonilimab as a first-in-class IO rescue agent, with the potential to carve out a distinct label in second-line HCC care.

How is Akeso structuring its broader cadonilimab development program beyond this trial?

The COMPASSION-36 study is one of multiple ongoing or completed registrational programs involving cadonilimab in HCC. In addition to this trial targeting second-line systemic therapy, Akeso has completed patient enrollment in a Phase III trial evaluating cadonilimab as adjuvant therapy for high-risk recurrence following curative surgery for HCC.

Another major study is underway evaluating a triplet regimen of cadonilimab + lenvatinib + transarterial chemoembolization (TACE) in intermediate to advanced unresectable HCC, addressing a patient population for whom systemic options remain sparse.

These trials reinforce Akeso’s multi-pronged clinical strategy to position cadonilimab across the treatment continuum—from neoadjuvant and adjuvant settings to late-stage systemic rescue. Analysts observing this strategy point to Akeso’s ability to rapidly translate preclinical rationales into clinical-stage evaluations across geographies.

What does cadonilimab’s trial expansion say about Akeso’s global ambitions and clinical innovation strategy?

Founded in 2012, Akeso has steadily built a reputation as one of China’s most internationally minded biopharma players. The launch of COMPASSION-36 across three continents underscores the company’s intent to scale its homegrown biologics platform to global regulatory and clinical expectations.

Cadonilimab is the flagship molecule in Akeso’s proprietary Tetrabody platform, designed for bispecific antibody development. The platform supports streamlined development of multifunctional molecules with reduced immunogenicity and improved efficacy profiles.

From an institutional view, Akeso’s dual-track strategy—in-house development coupled with global collaboration—mirrors the emerging model favored by Chinese biotechs seeking to leapfrog into Western markets. This approach allows Akeso to retain IP control while integrating best-in-class global resources for trial execution, regulatory consulting, and potential commercial partnerships.

The firm’s pipeline includes over 50 biologic assets, with 24 in clinical stages and 15 involving bispecific or multispecific constructs. With seven commercial-stage drugs already approved in China, Akeso is now pivoting hard into the international expansion phase.

What does the investment and regulatory outlook look like for cadonilimab and Akeso in the near term?

While Akeso has not yet disclosed projected timelines for submission of regulatory filings linked to COMPASSION-36, analysts expect potential fast-track or breakthrough designation applications if early data confirm superior outcomes over lenvatinib monotherapy. The FDA and NMPA have shown increasing receptiveness to IO assets addressing major unmet needs in tumor types like HCC.

Investor sentiment around cadonilimab remains cautiously optimistic. Given the limited commercial precedent for bispecifics in HCC, market observers are closely watching early efficacy and safety trends from registrational trials. That said, the absence of second-line standards in this setting means that any success could yield first-mover advantage and orphan-drug-type dynamics.

Akeso’s Hong Kong-listed shares (HKEX: 9926.HK) have seen modest volatility in recent quarters as the company transitions from a domestic focus to global-scale execution. The outcome of COMPASSION-36 could play an outsized role in validating Akeso’s next decade of growth.

How does cadonilimab reflect the broader evolution of immunotherapy in solid tumors like liver cancer?

The development arc of cadonilimab reflects a broader shift in oncology drug development—from monospecific checkpoint inhibitors to multi-pathway, bispecific and trispecific antibodies designed to outmaneuver tumor immune escape.

For hepatocellular carcinoma, which remains one of the deadliest cancers globally with 865,000 new cases in 2022, the quest for improved durability of response is paramount. First-line IO combinations like atezolizumab and bevacizumab have improved survival but offer limited long-term disease control. Cadonilimab’s dual inhibition strategy represents a new frontier in immunological re-engagement post-checkpoint failure.

Should cadonilimab prove its worth in randomized, multicenter studies like COMPASSION-36, it could emerge not just as a promising product, but as a platform validator for Akeso’s entire bispecific antibody pipeline.