Zovegalisib for PIK3CA-Related Overgrowth Spectrum

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.