Strategic risk assessment in oncology: Utilizing single-agent activity to boost combination therapy approvals.

Background: This study examines whether single-agent activity in early clinical phases correlates with the approval likelihood of combination therapies in oncology. Using the Intelligencia AI database, we investigated the impact of monotherapy efficacy on the success rates of combination therapies. Methods: The analysis included combinational therapies across various solid tumor types, assessing the approval rates and the presence of monotherapy efficacy with cut-off date September 12, 2024, and an assessment of 3896 programs. We analyzed historical clinical trial data focusing on Objective Response Rate (ORR) as a metric of single-agent activity (SAA). Results: Approval rate for combination programs across all indications and phases was 4.2 %. Programs that included approved monotherapy drugs had an approval rate of 6.1 %, whereas those without approved monotherapy drugs had a lower approval rate of 2.7 %. However, the historical approval rate for combination programs with failed monotherapy drug with more than 20 % objective response rate was 5.8 %. Furthermore, approved combinations derived from monotherapy-failed pipelines showed diverse ORR thresholds, with specific trends observed across different cancer types. Conclusions: The likelihood of approval for combination therapies is higher when combined with monotherapy drugs that have previously shown single agent activity. This finding is consistent with other research on historical approval rates and the common consensus within oncology drug development. Here we suggest that by leveraging monotherapy drug activity there can be an enhanced prioritization of anti-cancer agents repurposed for combination therapies, which would have otherwise been shelved based on their single agent failure.