Innovent Biologics has made the case that its checkpoint inhibitor-cytokine fusion protein has a future in colorectal cancer. A phase 1 trial that combined the drug candidate with Avastin reported a 21.9% response rate, including signs of efficacy in patients with liver metastases and prior immunotherapy use.
The candidate, IBI363, is designed to block the PD-1/PD-L1 pathway, unleashing similar effects to drugs such as Keytruda, and engage the IL-2 pathway to activate tumor-specific T cells. Multiple groups have identified IL-2 as a way to overcome PD-1 resistance but the field has been defined by failures so far, most notably Bristol Myers Squibb’s expensive misadventure with Nektar Therapeutics.
Innovent has continued to advance IBI363, which differs from earlier efforts in that it combines the PD-1 and IL-2 agents in a single molecule, even as other companies have pulled back from cytokine R&D. The biotech’s efforts have generated a body of early-phase data on the efficacy of IBI363.
In its latest update at the European Society for Medical Oncology 2024 Congress, Innovent reported data on 35 advanced colorectal cancer patients who received IBI363 and Avastin at one of three doses. The biotech saw a 21.9% response rate in the 32 patients who were evaluable for efficacy. Removing the unconfirmed responses, the response rate fell to 15.6%.
The median duration of response and progression-free survival were 8.1 months and 4.1 months, respectively. The study was yet to reach the median overall survival as of the data cutoff at the end of August.
Innovent shared response rate data in several subgroups. The response rate was lower in people with liver metastases, 11.8%, than without, 33.3%, but there were signs of activity in both groups. Innovent saw a higher response rate in patients who had previously received immunotherapy, 25%, than in the IO-naive group. However, the prior immunotherapy group only included eight patients.
With investigators seeing responses in patients with and without KRAS/NRAS exon 2/3/4 mutations, and safety aligning with expectations set in monotherapy studies, Innovent sees a future for its molecule in colorectal cancer. The biotech is also studying the candidate in indications such as non-small cell lung cancer, a setting in which it reported phase 1 data in June.