ESMO: Innovent ties cytokine fusion protein to colorectal cancer responses

Innovent Biologics has presented promising data indicating that its checkpoint inhibitor-cytokine fusion protein may have potential as a treatment for colorectal cancer. During a phase 1 clinical trial, the drug candidate, IBI363, was combined with Avastin and administered to a group of 35 patients with advanced colorectal cancer. The trial results revealed a 21.9% response rate among the 32 patients evaluable for efficacy, with indications of effectiveness in patients who had liver metastases and those previously treated with immunotherapy.

IBI363 is engineered to inhibit the PD-1/PD-L1 pathway, similar to established drugs like Keytruda, while also engaging the IL-2 pathway to stimulate tumor-specific T cells. While multiple researchers have explored IL-2 as a mechanism to counteract PD-1 resistance, the area has been fraught with challenges, such as the costly setbacks experienced by Bristol Myers Squibb with Nektar Therapeutics. Despite the broader industry trend of reducing cytokine research and development, Innovent has continued to invest in advancing IBI363. This perseverance has yielded early-phase data demonstrating the drug’s effectiveness.

At the European Society for Medical Oncology 2024 Congress, Innovent disclosed the latest findings from their study involving 35 advanced colorectal cancer patients treated with IBI363 and Avastin at one of three dose levels. Among the 32 patients available for assessment, the response rate was 21.9%. When excluding unconfirmed responses, the rate adjusted to 15.6%. The median duration of response and progression-free survival were recorded at 8.1 months and 4.1 months, respectively. By the end of August, the study had not yet established the median overall survival.

The response rate data also highlighted several subgroup analyses. Patients with liver metastases exhibited a lower response rate of 11.8% compared to 33.3% in those without liver metastases, yet there were signs of activity in both groups. Additionally, patients who had previously undergone immunotherapy showed a higher response rate of 25%, although this subgroup consisted of only eight patients.

Further analysis revealed responses in patients regardless of the presence of KRAS/NRAS exon 2/3/4 mutations, and the safety profile of IBI363 was consistent with expectations based on previous monotherapy studies. These findings support Innovent's belief in the potential of IBI363 for treating colorectal cancer. Beyond colorectal cancer, Innovent is also evaluating IBI363 in other conditions, such as non-small cell lung cancer, for which early-phase data were reported in June.