A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation (The ReInspire Study)

NCT06789913 · tracked via the Priya Life Science UK tracker

Sponsor

Relay Therapeutics, Inc.

Phase

Phase 2

Started

2025-06-13

Last updated

2026-08-25

Condition(s) studied

PIK3CA-Related Overgrowth Spectrum (PROS)Lymphatic MalformationsVascular MalformationsPIK3CA MutationCLOVES SyndromeKlippel Trenaunay SyndromeMegalencephaly-capillary Malformation Polymicrogyria Syndrome (MCAP)Vascular Anomalies

Investigational drug(s) / intervention(s)

RLY-2608Placebo

RLY-2608: RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.

Placebo: RLY-2608 matched-placebo

Study summary

This is a 3-part Phase 2 randomized study evaluating the safety and efficacy of the mutant-selective PI3Kα inhibitor, zovegalisib (RLY-2608), in adults and children with PIK3CA Related Overgrowth Spectrum (PROS) and malformations driven by PIK3CA mutation. Part 1 is a dose selection, Part 2 is a basket design with exploratory single-arm cohorts for various subpopulations of participants, and Part 3 is randomized, double-blinded study vs placebo.

Eligibility

Sex

ALL

Min age

2 Years

Max age

—

Healthy volunteers

Key Inclusion Criteria: * The participant must have a clinical diagnosis of PROS or a malformation within the ISSVA classification. * One or more documented activating PIK3CA mutation(s) that are targeted by selective PI3Kα inhibitors in lesional tissue and/or cell-free DNA from the lesion or blood. Some participants may be eligible without a documented PIK3CA mutation, with the sponsor's approval, as long as no other genetic driver has been documented. * Lansky (\<16 yo) or Karnofsky (≥16 yo) performance status of ≥50. * Agree to provide archived lesional fluid and/or tissue or be willing to undergo pretreatment lesional biopsy (if considered safe and medically feasible) to assess PIK3CA status. Key Exclusion Criteria: * Known hypersensitivity to RLY-2608. * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events * Clinically significant, uncontrolled cardiovascular disease * Received disease-directed therapy prior to the first dose of study drug: 1. Systemic therapy or antibody within 5 half-lives of the therapy. 2. Local therapy including radiation, surgery, or other procedures within 28 days; lesion(s) must have demonstrated progression after the procedure.

Primary outcome measure(s)

Parts 1 and 2: Determination of a recommended phase 2 dose RP2D(s) for Groups 1, 2, and 3 — Cycle 1 of treatment and at the end of every cycle until study discontinuation
Parts 1 and 2: Occurrence/frequency of Adverse Events (AEs), changes in vital signs, ECGs, and safety laboratory tests and their relationship to the study drugs (safety and tolerability). — Cycle 1 of treatment and at the end of every cycle until study discontinuation
Part 3: Percentage of participants with volumetric Response. — Baseline, Week 24

Trial sites (40)

Facility	City	Region	Status
Phoenix Children's Hospital	Phoenix	Arizona	Recruiting
Arkansas Children's Hospital	Little Rock	Arkansas	Recruiting
University of California, Los Angeles	Los Angeles	California	Recruiting
Stanford University	Palo Alto	California	Recruiting
University of California, San Francisco	San Francisco	California	Recruiting
Children's Hospital Colorado	Aurora	Colorado	Recruiting
Children's Hospital of Atlanta	Atlanta	Georgia	Recruiting
Riley Children's Hospital	Indianapolis	Indiana	Recruiting
University of Iowa	Iowa City	Iowa	Recruiting
Johns Hopkins Medical Institute	Baltimore	Maryland	Recruiting
Boston Children's Hospital	Boston	Massachusetts	Recruiting
Corewell Health	Grand Rapids	Michigan	Recruiting
Mayo Clinic	Rochester	Minnesota	Recruiting
Washington University School of Medicine	St Louis	Missouri	Recruiting
NYU Langone Health	New York	New York	Recruiting
UNC Chapel Hill	Chapel Hill	North Carolina	Recruiting
Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	Recruiting
Cleveland Clinic Children's	Cleveland	Ohio	Recruiting
Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	Recruiting
Texas Children's Hospital	Houston	Texas	Recruiting
Seattle Children's Hospital	Seattle	Washington	Recruiting
University of Wisconsin, Madison	Madison	Wisconsin	Recruiting
Sydney Children's Hospital, Randwick	Randwick	New South Wales	Recruiting
Children's Health Queensland Hospital and Health	South Brisbane	Queensland	Recruiting
Monash Health	Clayton	Victoria	Recruiting
Royal Melbourne Hospital	Parkville	Victoria	Recruiting
Murdoch Children's Research Institute	Parkville	Victoria	Recruiting
UC Louvain	Ottignies-Louvain-la-Neuve	Belgium	Recruiting
Necker Hospital	Paris	France	Recruiting
University of Halle	Halle	Germany	Recruiting
Children's Health Ireland at Crumlin	Dublin	Ireland	Recruiting
Ospedale Maggiore Policlinico	Milan	Italy	Recruiting
IRCCS Fondazione Policlinico Universitario A. Gemelli	Roma	Italy	Recruiting
Ospedale Pediatrico Bambino Gesù IRCCS	Roma	Italy	Recruiting
A.O.U Città della Salute e della Scienza di Torino	Torino	Italy	Recruiting
Hospital Universitario A Coruña	A Coruña	Spain	Recruiting
Hospital Sant Joan de Deu	Barcelona	Spain	Recruiting
Hospital Universitario La Paz	Madrid	Spain	Recruiting
Chelsea and Westminster Hospital	London	United Kingdom	Recruiting
Great Ormond Street Hospital for Children	London	United Kingdom	Recruiting

More Relay Therapeutics, Inc. trials in the UK

Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer Recruiting

Other trials for the same condition

Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer Recruiting

Study Assessing the Efficacy, Safety and PK of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum Active, not recruiting

Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation. Recruiting

EPIK-P4: A Phase II Single-arm Study to Assess the Efficacy, Safety and Pharmacokinetics of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (PROS) Recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06789913 on ClinicalTrials.gov ↗ ← All trials in the UK