Relay Therapeutics has reported promising Phase 2 ReInspire trial results for zovegalisib in PIK3CA-driven vascular anomalies, showing meaningful efficacy, broad patient-reported improvements, and a favorable safety profile that may differentiate it from earlier PI3Kα inhibitors.
Written By: Dr. Preethi Putti, PharmD
Reviewed By: Pharmacally Editorial Team
Relay Therapeutics has reported encouraging initial clinical data from its ongoing Phase 2 ReInspire trial (NCT06789913) evaluating zovegalisib in patients with PIK3CA-driven vascular anomalies. The findings, presented at the ISSVA World Congress 2026, suggest the investigational therapy may provide meaningful efficacy alongside manageable long-term tolerability in patients with rare and debilitating vascular disorders that currently lack broadly effective targeted therapies.
The study is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of zovegalisib across multiple age groups. As of the April 15, 2026 data cutoff, 32 patients aged 12 years and older had been randomized across three dose cohorts: 100 mg BID (n=11), 300 mg BID (n=11), and 400 mg BID (n=10).
Among the 20 response-evaluable patients who reached the first MRI assessment at 12 weeks, 60% achieved a volumetric response, defined as at least a 20% reduction in lesion volume. Nearly all patients experienced some degree of lesion shrinkage. Responses were observed across multiple PIK3CA mutation types and disease subgroups, including PIK3CA-related overgrowth spectrum (PROS) and lymphatic malformations (LM). Responses were also reported among patients previously treated with alpelisib and/or sirolimus.
Relay has opened Part 2 expansion cohorts for patients aged 12 years and older at 400 mg once daily and 300 mg BID, reflecting a shift toward lower-dose regimens intended to support chronic treatment. Part 3 of the study may potentially incorporate a randomized design to further evaluate comparative efficacy.
Patient- and investigator-reported outcomes also showed broad clinical improvement. At week 12, 89% of patients demonstrated improvement based on investigator global impression scores, while 79% reported improvement through patient global impression assessments. Improvements in pain-related symptoms were observed in 71% of assessments.
Safety findings supported continued development of lower-dose regimens. Among the 22 patients treated at 100 mg or 300 mg BID, dose reductions occurred in 23% of patients, with no treatment discontinuations due to adverse events. Median dose intensity exceeded 99%, and only 9% experienced Grade 3 or higher treatment-related adverse events. No rash, stomatitis, Grade 3 hyperglycemia, or severe diarrhea were reported.
The tolerability profile may differentiate zovegalisib from earlier PI3Kα inhibitors such as alpelisib, which are often associated with hyperglycemia and rash. Zovegalisib is also under evaluation in the Phase 3 ReDiscover-2 trial in PI3Kα-mutated HR-positive/HER2-negative advanced breast cancer.
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About the Writer
Dr.Preethi Putti, PharmD (LinkedIn) is a pharmaceutical researcher with experience in healthcare and pharmaceutical market research and competitive intelligence. She specializes in analyzing drug pipelines, clinical data, and industry trends and translating complex scientific data into clear and structured medical content. Strong foundation in clinical research, data interpretation, and evidence-based healthcare analysis. Committed to advancing a global career in clinical research and healthcare innovation.