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

Key Inclusion Criteria:

• The participant must have a clinical diagnosis of PROS or a malformation within theISSVA 2018 classification.

• One or more documented activating PIK3CA mutation(s) that are targeted by selectivePI3Kα inhibitors in lesional tissue and/or cell-free DNA from the lesion or blood

• Lansky (<16 yo) or Karnofsky (≥16 yo) performance status of ≥50.

• Agree to provide archived lesional fluid and/or tissue or be willing to undergopretreatment lesional biopsy (if considered safe and medically feasible) to assessPIK3CA 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 within 5 half-lives of the drug or 14 days, whichever islonger and received antibody therapy within 28 days.

2. Local therapy including radiation, surgery, or other procedures within 28 days;lesion(s) must have demonstrated progression after the procedure.