Onconova Therapeutics’ early-phase development program for the multikinase inhibitor narazaciclib has cleared a small milestone, with the lack of dose-limiting toxicities in solid tumor patients in the original cohorts emboldening the biotech to plan to file a protocol amendment to study higher doses.
The program consists of phase 1 dose-escalation trials in China and the U.S. Onconova is now enrolling patients in the fourth-dose cohort in the U.S. and in the fifth-dose cohort in China. As there have been no dose-limiting toxicities in either study, Onconova is preparing to ask the Chinese regulator to allow it to study doses above the 200 mg it is currently giving to patients in the fifth-dose cohort.
Onconova’s U.S. trial lacks the 200-mg dose ceiling baked into the Chinese study, allowing it to continue going up in 40-mg increments without filing a protocol amendment. However, other differences between the studies mean Onconova may reach a dose-limiting toxicity earlier than in the Chinese clinical trial.
In China, Onconova has a three-week on, one-week off protocol, whereas in the U.S. Onconova is using a daily dosing schedule for its CDK4/6 inhibitor. Onconova CEO Steve Fruchtman set out the reasons for the different designs and their potential implications for the data on a fourth-quarter results conference call with investors.
“Because it’s every day dosing, the results can be different. We designed the trial this way to mimic the way CDK4/6 inhibitors are prescribed in the U.S.—two of the drugs prescribed three-week on, one-week off, one of the drugs prescribed daily—and we don’t know what will be required to optimize the recommended phase 2 dose of narazaciclib,” Fruchtman said.
The program is central to Onconova’s efforts to recover from the failures of its other asset rigosertib. In 2014, the drug, then partnered with Baxter, failed a phase 3 myelodysplastic syndrome trial. Onconova pushed on only to flunk another phase 3 study in 2020.