Promising Results of Cadonilimab and Pulocimab in Treating Resistance in Lung Cancer

Promising Results of Cadonilimab and Pulocimab in Treating IO-Resistant Lung Cancer

In a groundbreaking development presented at the 2025 World Conference on Lung Cancer (WCLC), Akeso Inc. revealed compelling results from their Phase Ib/II clinical study on a combination therapy using cadonilimab (PD-1/CTLA-4) and pulocimab (VEGFR-2). This combination aims to offer a new therapeutic option for patients suffering from non-small cell lung cancer (NSCLC) who are resistant to immunotherapy (IO).

The significance of this data lies in its position as the first clinical evidence for cadonilimab in treating IO-resistant NSCLC. Previously granted Breakthrough Therapy Designation by the National Medical Products Administration (NMPA), this combination therapy is particularly aimed at patients with advanced squamous NSCLC who have shown progression after treatment with PD-(L)1 inhibitors.

The findings at the WCLC highlighted that the cadonilimab-pulocimab combination is not just another treatment but a promising chemo-free approach for advanced IO-resistant NSCLC patients. The clinical data demonstrated encouraging efficacy and broad potential for patients who have already undergone first-line standard immunotherapy-based treatments. In essence, for patients grappling with this aggressive form of cancer, this might represent a significant leap in therapeutic options.

As of January 13, 2025, data revealed that with a median follow-up of 16.7 months, those treated with the cadonilimab combination achieved a median overall survival (mOS) of 15.6 months and a median progression-free survival (mPFS) of 5.8 months. Notably, in the subgroup of squamous NSCLC patients, results were even more promising, with an mOS of 16.7 months and mPFS of 7.1 months, achieving an impressive Disease Control Rate (DCR) of 96.2% and an Objective Response Rate (ORR) of 11.5%. In contrast, outcomes for the non-squamous NSCLC subgroup were recorded at an mOS of 12.8 months and an mPFS of 5.5 months.

The data not only underscores the promising clinical efficacy of this combination but also emphasizes Akeso's commitment to advancing treatment options for cancer patients. With the ongoing preparations for a Phase III clinical trial, the future looks optimistic for this duo as a frontline therapy against IO-resistant lung cancer.

Moreover, Akeso's innovative approach is not limited to these two agents. The company is making strides with their second bispecific antibody, ivonescimab (PD-1/VEGF), which has also shown remarkable efficacy in the IO-resistant NSCLC demographic. Notably, a registrational Phase III trial for ivonescimab is already underway, indicating robust advancement in the therapeutic landscape.

As first-in-class bispecific antibodies, cadonilimab and ivonescimab hold the potential to address the pressing challenges of resistance commonly seen with traditional single-target treatments, such as PD-1 inhibitors. By targeting multiple pathways in the immune response, these treatments aim to deliver enhanced efficacy, reinforcing Akeso’s position as a leader in biopharmaceutical innovation.

Over recent years, immunotherapy has dramatically changed lung cancer treatment dynamics. Given that an alarming 60%–70% of lung cancer patients experience disease progression within a year, finding effective second-line treatments is paramount. Standard therapies like docetaxel have had limited efficacy, and there is currently no approved standard treatment for NSCLC after IO resistance.

The emergence of cadonilimab and pulocimab as viable options may represent a crucial evolution in treating this challenging patient population. Additionally, the potential efficacy seen in the treatments for other resistant cancers, including hepatocellular carcinoma and gastric cancer, suggests that this therapy might serve a wider range of patients falling under the IO-resistant category.

With breakthroughs like these, patients struggling with cancer have a glimmer of hope as Akeso continues to push boundaries in research and drug development. Their commitment to developing first-in-class and best-in-class treatments is reshaping the future of oncology, ensuring that both clinical needs and patient survival rates are prioritized. As they forge ahead, the ultimate aim is to provide accessible and effective therapeutic options that challenge the prevailing limitations faced by cancer patients today.