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

About

Brief Summary

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. 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.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 2

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

2 Years

Maximum Age

N/A

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:
- Systemic therapy or antibody within 5 half-lives of the therapy.
- Local therapy including radiation, surgery, or other procedures within 28 days; lesion(s) must have demonstrated progression after the procedure.