Akeso begins Phase 3 trial of cadonilimab as consolidation therapy for non-small cell lung cancer

Akeso, Inc. (9926.HK) has initiated its pivotal Phase 3 cadonilimab trial for non-small cell lung cancer (NSCLC), marking a significant advancement in immunotherapy research. The study, officially titled COMPASSION-30/AK104-309, aims to evaluate the efficacy of cadonilimab as a consolidation therapy in patients with locally advanced, unresectable NSCLC who have not experienced disease progression following concurrent or sequential chemoradiotherapy.

This randomized, double-blind, multicenter Phase 3 trial will compare cadonilimab, a PD-1/CTLA-4 bispecific antibody, against sugemalimab, a PD-L1 inhibitor, to determine which therapy provides superior long-term survival benefits. The trial is being led by Prof. Jinming Yu, an academician at the Chinese Academy of Engineering and director of the Oncology Hospital at Shandong First Medical University.

How Could Cadonilimab Improve NSCLC Consolidation Therapy?

For patients with unresectable NSCLC, consolidation therapy has become a critical component of treatment, particularly after initial chemoradiotherapy. Immune checkpoint inhibitors (ICIs), such as PD-1 and PD-L1 inhibitors, have demonstrated the ability to enhance immune responses against tumors, resulting in modest improvements in overall survival. However, many patients still experience disease recurrence or limited therapeutic benefits, highlighting the urgent need for more effective immunotherapy options.

Cadonilimab is an innovative PD-1/CTLA-4 bispecific antibody, designed to enhance immune responses beyond conventional PD-1/PD-L1 inhibitors. The therapy works by blocking two key immune checkpoints, PD-1 and CTLA-4, allowing T cells to remain active for longer durations, thereby intensifying the immune system’s ability to eliminate cancer cells. Unlike traditional single-target therapies, cadonilimab has a tetravalent symmetric structure with Fc modifications, enabling higher tumor-specific accumulation while minimizing immune-related side effects.

This structural advantage may position cadonilimab consolidation therapy as a more effective alternative to current standard-of-care ICIs, offering improved survival outcomes for NSCLC patients who have completed chemoradiotherapy.

What Are the Clinical Advancements of Cadonilimab?

Cadonilimab has already established itself as a breakthrough immunotherapy in oncology. The drug received its first regulatory approval in June 2022 from China‘s National Medical Products Administration (NMPA) for the treatment of recurrent or metastatic cervical cancer in patients who had progressed on platinum-based chemotherapy. This approval marked cadonilimab as the world’s first PD-1/CTLA-4 bispecific antibody to enter the commercial market.

In September 2024, cadonilimab was further approved in China as a first-line treatment for unresectable, locally advanced, recurrent, or metastatic gastric and gastroesophageal junction (G/GEJ) adenocarcinoma. Its expanding clinical applications reflect growing confidence in bispecific immunotherapies as a next-generation approach to cancer treatment.

Akeso is currently advancing over 23 clinical trials exploring cadonilimab combination therapies across 16 indications, including cervical, gastric, liver, and lung cancer. The results of the Phase 3 cadonilimab trial for NSCLC will be closely monitored, as its success could solidify cadonilimab’s role in lung cancer treatment and further expand its global market potential.

Why Is There an Unmet Need for Advanced NSCLC Therapies?

Despite significant progress in lung cancer treatment, many patients with locally advanced NSCLC still face poor long-term survival prospects. Standard chemoradiotherapy followed by immune checkpoint inhibition has led to some survival benefits, but these gains remain limited for a substantial portion of patients.

The complexity of tumor microenvironments and the adaptive immune resistance mechanisms of NSCLC make it difficult for single-agent immunotherapies to deliver sustained responses. Cadonilimab’s dual checkpoint blockade has the potential to reshape the immune response landscape, offering a more comprehensive approach to tumor eradication.

Furthermore, while PD-1 and PD-L1 inhibitors have dominated the immunotherapy landscape, their effectiveness can vary based on tumor mutation burden, microenvironment factors, and patient-specific immune responses. PD-1/CTLA-4 bispecific antibodies like cadonilimab aim to overcome these limitations, offering a multifaceted immune activation approach that could improve overall treatment efficacy.

What Impact Could This Trial Have on Global Cancer Research?

If successful, the cadonilimab Phase 3 trial for NSCLC consolidation therapy could have wide-reaching implications for cancer immunotherapy. The results may not only influence treatment guidelines for lung cancer but could also drive further research into bispecific antibody therapies across multiple oncology indications.

Akeso’s ability to advance cadonilimab as a first-in-class PD-1/CTLA-4 bispecific antibody underscores its commitment to pioneering cancer treatments that extend beyond traditional checkpoint inhibitors. As global interest in bispecific immunotherapy grows, Akeso’s continued progress in clinical development could position it as a leader in next-generation oncology drug development.

The success of this trial may also impact international regulatory discussions, as global health authorities assess the clinical benefits of bispecific immunotherapies compared to existing monotherapies. Given the increasing demand for innovative treatment solutions, cadonilimab’s potential approval for NSCLC could pave the way for wider adoption of dual checkpoint blockade strategies in oncology.

What’s Next for Cadonilimab and Akeso?

With its ongoing global expansion and multiple active trials, Akeso is positioning itself as a key player in the competitive immunotherapy market. The company’s continued investment in bispecific antibody research reflects a strategic focus on developing cutting-edge cancer therapies with broad clinical applications.

If the cadonilimab Phase 3 trial for NSCLC consolidation therapy delivers positive results, Akeso could take a significant step toward securing global approvals and establishing cadonilimab as a cornerstone treatment in lung cancer immunotherapy.

The oncology community will be closely monitoring the outcomes of this trial, as its success could shape the future of next-generation immune checkpoint inhibitors and reinforce the role of bispecific antibody therapies in lung cancer treatment advancements.