Adding IO Biotech’s lead candidate, IO102, to first-line treatment with Keytruda (pembrolizumab) is likely to result in better response rates in people with metastatic non-small cell lung cancer (NSCLC), an interim analysis of a Phase 2 trial showed.
The analysis, with predetermined requirements and called a futility analysis, determines whether a trial will likely meet its goals, and either supports its continuation or it being stopped.
Based on these findings, the study’s independent data monitoring committee recommended the trial continue without modifications.
“The successful outcome of this interim analysis required the objective response rate in the experimental arm [IO102-Keytruda combination therapy] to exceed the futility boundary which was substantially higher than the historical experience with Keytruda monotherapy in this population,” Eva Ehrnrooth, MD, PhD, IO Biotech’s chief medical officer, said in a press release.
“We are excited to note that this hurdle has been successfully crossed,” Ehrnrooth added.
IO102 is a second generation immune-modulating vaccine that targets indolamine 2,3 dioxygenase (IDO), an enzyme highly present in cancer cells — as a mechanism to evade anti-tumor responses — and in immunosuppressive cells.
By promoting immune reactions against IDO, IO102 targets cancer cells directly and indirectly, since eliminating immunosuppressive cells within the tumor microenvironment also increases natural responses against tumor cells. IO102, an anti-cancer vaccine, is given as an under-the-skin injection.
This approach is thought to have the best potential when combined with an immune checkpoint inhibitor, such as Keytruda. Marketed by Merck (known as MSD outside the U.S. and Canada), Keytruda is approved, as a single therapy or in combination with chemotherapy, to treat advanced NSCLC.
Keytruda works by preventing another immune evasion mechanism, one involving the interaction between the PD-1 receptor in immune T-cells and its ligand PD-L1 in cancer cells. By preventing this interaction, the therapy boosts T-cells’ ability to detect and fight tumor cells.
The open-label Phase 1/2 clinical trial, known as IO102-012/KEYNOTE-764 (NCT03562871), is evaluating the safety and effectiveness of combining IO102 with Keytruda — with or without chemotherapy — as first-line treatment for people with metastatic NSCLC.
The trial, which is still enrolling, aims to recruit about 110 patients at sites across Europe and, the company reports, in the U.S. as well.
The study’s Phase 1 part was meant to determine the combo’s safety. Phase 2 aims primarily to assess whether adding IO102 to Keytruda — with or without chemotherapy — leads to superior rates of response (partial and complete responses) than Keytruda alone, again with and without chemotherapy. Secondary goals include the response rate in patients with different levels of PD-L1 (measured at the study’s start).
In Phase 2, patients will be treated for up to two years, corresponding to 35 therapy cycles, each spaced three weeks apart. Primary data collection is expected to be completed in November.
“Through this trial, we expect to get a comprehensive data set that paves the way for a potential pivotal trial of IO102 addressing the unmet medical need in NSCLC and solid tumors,” Ehrnrooth said.
Mai-Britt Zocca, PhD, IO Biotech’s CEO and founder, said the company is “pleased” by KEYNOTE-764’s data so far.
“We continue to demonstrate long term durability of [therapy] effect with a very attractive safety profile for each of our clinical stage candidates, whether alone or in any combination,” Zocca added.
KEYNOTE-764 is being sponsored and conducted by IO Biotech, while Merck provides Keytruda. The rights to its results will be shared by the two companies.
