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

Study of Investigational Medication for PIK3CA Related Overgrowth Spectrum

R
Rachael Schulte

Primary Investigator

Enrolling By Invitation
2 years or above
All
Phase 2
1 participants needed
2 Locations

Brief description of study

This is a 3-part Phase 2 randomized study evaluating the safety and efficacy of the mutant-selective PI3Kα inhibitor, RLY-2608, in adults and children with PIK3CA Related Overgrowth Spectrum (PROS) and malformations driven by PIK3CA mutation. 

THIS STUDY IS ENROLLING BY INVITATION ONLY

Detailed description of study

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 of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: CLOVES Syndrome, Klippel Trenaunay Syndrome, Lymphatic Malformations, Megalencephaly-capillary Malformation Polymicrogyria Syndrome (MCAP), PIK3CA Mutation, PIK3CA-Related Overgrowth Spectrum (PROS), Vascular Malformations, Riley
  • Age: 2 years or above
  • Gender: All

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.

This study investigates a treatment for PIK3CA Related Overgrowth Spectrum (PROS), a condition caused by a mutation in the PIK3CA gene that leads to abnormal growths in the body. The purpose of this study is to evaluate the safety and effectiveness of an investigational medication targeting these mutations.

Participants in this study will be randomly assigned to different study arms. Some will receive the investigational medication, while others will receive a placebo, which is an inactive substance that looks like the investigational medication but does not contain any medicine. The study will include various procedures to monitor the effects of the treatment.

  • Who can participate: Adults and children with a clinical diagnosis of PROS or specific malformations can participate. Eligibility requires a PIK3CA mutation or no other genetic driver, willingness to provide tissue samples, and meeting certain health criteria.
  • Study details: Participants will be required to provide tissue samples and may undergo a biopsy. They will be assigned to receive either the investigational medication or a placebo.
Updated on 05 Feb 2026. Study ID: PHO-RTI-RLY-2608-201, 28169
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Interested in the study?

This study is accepting only persons who receive care at a certain clinic or doctor or who are part of an invited group. Questions about this study can be directed to the study team listed in the description or contact your doctor to see if you are eligible.

Accepting Referrals by Invitation Only