Akeso announced the publication of the phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab (PD-1/CTLA-4 bispecific antibody) in patients with advanced solid tumors in Cell Reports Medicine, a sub-publication of Cell. The study findings revealed that cadonilimab reached a dose of 25 mg/kg every 3 weeks (Q3W) without encountering the maximum tolerated dose (MTD). The occurrence of severe immune-related adverse events (irAE) with a grade of 3 or higher was only 6.7%.

These results indicate that cadonilimab exhibits a favorable safety and tolerability profile in the treatment of advanced solid tumors. Based on the study, a recommended dose of 6 mg/kg every 2 weeks (Q2W) was established. Remarkably, tumor response was observed in both PD-L1-positive and PD-L1-negative solid tumor populations, indicating that cadonilimab possesses unique efficacy advantages over PD-1/PD-L1 monoclonal antibodies and may have a broader range of potential indications.

In conclusion,cadonilimab was found to have a favorable toxicity profile and promising efficacy for patients with solid tumors that were refractory/relapsed to standard therapies or for which no effective standard therapy was available. Cadonilimab has been approved by the China National Medical Products Administration (NMPA) for recurrent or metastatic cervical cancer. Currently, Akeso has initiated/conducted a series of more than 60 clinical studies globally for patients with solid tumors that were refractory/relapsed to standard therapies or for which no effective standard therapy was available, covering more than 20 types of malignant tumors, including gastric cancer, hepatocellular carcinoma, lung cancer, cervical cancer, pancreatic cancer, renal cancer, esophageal squamous carcinoma, colorectal cancer, nasopharyngeal carcinoma, pleural mesothelioma, and other malignant tumors.

About Cadonilimab(PD-1/CTLA-4 bispecific antibody): Cadonilimab is a first-in-class bispecific antibody that targets both PD-1 and CTLA-4 developed by Akeso. It is a symmetric tetravalent bispecific antibody with a crystallizable fragment (Fc)-null design. In addition to demonstrating biological activity similar to that of the combination of CTLA-4 and PD-1 antibodies, cadonilimab possesses higher binding avidity in a high-density PD-1 and CTLA-4 setting than in a low-density PD-1 setting, while a mono-specific anti-PD-1 antibody does not demonstrate this differential activity.

With no binding to Fc receptors, cadonilimab shows minimal antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and interleukin-6 (IL-6)/IL-8 release. These features all likely contribute to significantly lower toxicities of cadonilimab observed in the clinic. Higher binding avidity of cadonilimab in a tumor-like setting and Fc-null design may lead to better drug retention in tumors and contribute to better safety while achieving anti-tumor efficacy.

Cadonilimab has been approved by the China National Medical Products Administration for recurrent or metastatic cervical cancer. Cadonilimab has been included and recommended in multiple clinical guidelines such as CSCO. In its first 12 months on the market, cadonilimab generated impressive sales revenue of 1.15 billion RMB.

Cadonilimab has been engaged in more than 60 ongoing clinical trials including investigator-initiated studies. Patient enrollment has been completed for the phase 3 study of cadonilimab for first-line treatment of advanced cervical cancer as well as a phase 3 study of cadonilimab in combination with chemotherapy as first-line therapy in gastric cancer. A phase 3 study of cadonilimab as an adjuvant treatment for hepatocellular carcinoma is ongoing.

Furthermore, a Phase III study comparing cadonilimab with chemotherapy to tislelizumab Injection with chemotherapy is underway for the first-line treatment of PD-L1 expression-negative non-small cell lung cancer.