Health Trials

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)

ConditionsPIK3CA-Related Overgrowth Spectrum (PROS)Lymphatic MalformationsVascular MalformationsPIK3CA MutationCLOVES SyndromeKlippel Trenaunay SyndromeMegalencephaly-capillary Malformation Polymicrogyria Syndrome (MCAP)Vascular Anomalies
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age2+
SponsorRelay Therapeutics, Inc.

About this trial

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 criteria

Qualifiers

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.

Disqualifiers

Known hypersensitivity to RLY-2608.

Any factors that increase the risk of QTc prolongation or risk of arrhythmic events

Clinically significant, uncontrolled cardiovascular disease

Systemic therapy or antibody within 5 half-lives of the therapy.

Trial design

Treatments tested in this trial

  • RLY-2608
  • Placebo

Treatment groups

277 Participants
are divided into 8 treatment groups

8

Treatment groups

See each treatment group below.

Locations

34
Australia
Sydney Children's Hospital, Randwick2031, RandwickNew South Wales, Australia
Children's Health Queensland Hospital and Health4101, South BrisbaneQueensland, Australia
Monash Health3168, ClaytonVictoria, Australia
Murdoch Children's Research Institute3052, ParkvilleVictoria, Australia

Sponsors and collaborators

Relay Therapeutics, Inc.

Lead sponsor

Source ClinicalTrials.gov