Relay Therapeutics has reported initial findings from its Phase II ReInspire trial evaluating zovegalisib in patients with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-driven vascular anomalies, underlining the role of PI3Kα mutant-selective inhibition.
The interim analysis focuses on adults and adolescents aged 12 years and above in the dose randomisation segment of the study.
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Vascular anomalies, involving abnormal blood or lymphatic vessel development, are rare disorders.
In this analysis, 60% of patients achieved a volumetric response at 12 weeks, the earliest assessment, while the majority experienced symptomatic improvement. Safety data indicated that zovegalisib could be suitable for long-term use.
Relay Therapeutics research and development president Don Bergstrom said: “These data demonstrate, for the first time, the promise of PI3Kα mutant-selective inhibition for patients with vascular anomalies.
“The combination of robust volumetric responses, symptomatic improvement, and a safety profile that supports chronic dosing underscores the potential of zovegalisib to meaningfully change the treatment paradigm for this underserved population.”
The trial includes adults, adolescents, and paediatric patients aged two to 11 years with PIK3CA-mutated vascular anomalies.
The three-part design involves dose selection (Part I), dose expansion with open-label cohorts (Part II), and possibly a randomised study (Part III).
In Part I, 32 patients aged 12 years and above were enrolled and received 100mg, 300mg, or 400mg twice daily (BID).
This cohort included patients with PIK3CA-related overgrowth spectrum (PROS), lymphatic malformation (LM), and venous malformation (VeM), most of whom had prior sirolimus and/or alpelisib treatment.
Out of 20 efficacy-evaluable patients, 60% showed a volumetric response at the first magnetic resonance imaging (MRI) assessment, and 95% had some lesion reduction.
Responses were observed in both those with kinase and non-kinase mutations and among patients previously treated with other therapies. Four patients confirmed and deepened their response at 24 weeks.
The safety profile across doses ranged from 100mg to 400mg BID, aligning with expectations for mutant-selective PI3Kα inhibition. Dose reductions occurred in 23% of patients at 100mg and 300mg BID, with no discontinuations.
Grade 3 or higher adverse events were limited, and common side effects were manageable and reversible. The 400mg BID dose will not be developed further due to suboptimal tolerability.
