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Treatment for PIK3CA-related overgrowth and malformations using RLY-2608

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

PHASE2 · Relay Therapeutics, Inc. · NCT06789913

This study is testing a new treatment called RLY-2608 to see if it can help adults and children with PIK3CA-related overgrowth and malformations feel better.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment277 (estimated)
Ages2 Years and up
SexAll
SponsorRelay Therapeutics, Inc. (industry)
Drugs / interventionsradiation
Locations31 sites (Phoenix, Arizona and 30 other locations)
Trial IDNCT06789913 on ClinicalTrials.gov

What this trial studies

This Phase 2 study evaluates the safety and efficacy of RLY-2608, a mutant-selective PI3Kα inhibitor, in treating adults and children with PIK3CA Related Overgrowth Spectrum (PROS) and related malformations. The study consists of three parts: a dose selection phase, a basket design with exploratory cohorts for various subpopulations, and a randomized, double-blinded comparison against a placebo. Participants will be assessed for their response to the treatment based on their specific PIK3CA mutations. The study aims to provide targeted therapy for individuals affected by these conditions.

Who should consider this trial

Good fit: Ideal candidates include individuals with a clinical diagnosis of PROS or related malformations and documented activating PIK3CA mutations.

Not a fit: Patients with a history of hypersensitivity to PI3K inhibitors or significant cardiovascular issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the management of PIK3CA-related overgrowth conditions, leading to better health outcomes for affected patients.

How similar studies have performed: Other studies have shown promise with similar targeted therapies for PIK3CA mutations, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
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 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:

* History of hypersensitivity to PI3K inhibitors.
* 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.

Where this trial is running

Phoenix, Arizona and 30 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: PIK3CA-Related Overgrowth Spectrum, Lymphatic Malformations, Vascular Malformations, PIK3CA Mutation, CLOVES Syndrome, Klippel Trenaunay Syndrome, Megalencephaly-capillary Malformation Polymicrogyria Syndrome

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.