Akeso keeps cadonilimab in China

Last week at the Society of Gynecologic Oncology meeting Akeso presented impressive data with its anti-PD-1 x CTLA-4 bispecific cadonilimab in a phase 3 Chinese trial in first-line cervical cancer. The results could help the company expand the drug’s indications in China, but Akeso has no immediate plans to pursue US approval in this indication or others, a spokesperson has told ApexOnco.

The safety run-in phase of Compassion-18 found a 100% overall response rate, and an 85% complete response rate, among 33 patients receiving cadonilimab plus radiotherapy. Median progression-free survival hasn’t been reached, but the 12-month PFS rate was 75%.

Still, toxicity, which has been a problem with CTLA-4 inhibitors, was notable: 59% of patients had a grade 3 or higher adverse event related to cadonilimab, while 35% of patients discontinued owing to treatment-related adverse events. There were no treatment-related deaths, however, and the investigators concluded that the safety profile was acceptable. 

The next stage of the study will see patients randomised to cadonilimab plus radiotherapy, or radiotherapy alone, with a primary endpoint of PFS.

Cadonilimab was approved in China for second-line cervical cancer in 2022; the NPMA is also reviewing a supplemental NDA in first-line disease, based on the Compassion-16 study, which tested cadonilimab plus platinum-based chemotherapy, with or without Avastin.

No US progress

However, in the US things haven’t progressed since a global phase 2 cervical cancer trial completed in 2022. When asked about its plans stateside, Akeso told ApexOnco that “phase 3 research will not be moving forward” in this setting. Meanwhile, a small investigator-sponsored US phase 2 trial in cervical cancer is ongoing.

Across broader indications, the company is keeping an open mind, with the spokesperson flagging several phase 3 China studies, including in gastric, lung and liver cancers, adding: “Akeso will decide on US market development based on cadonilimab’s strengths and available resources.” She concluded that the project could be taken forward independently, or via a partner.

Last September, Akeso received Chinese approval for cadonilimab in first-line gastric/GEJ carcinoma irrespective of PD-L1 expression status, based on the Compassion-15 study.

PD-1 x CTLA-4 bispecifics have had their setbacks, with Xencor last month deprioritising vudalimab. However, AstraZeneca is in phase 3 with volrustomig, and MacroGenics just shifted focus to lorigerlimab, after disappointing with its previous lead asset, vobramitamab duocarmazine.