EPIK-P4: A Phase II Single-arm Study to Assess the Efficacy, Safety and Pharmacokinetics of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (PROS)

The study consists of a screening period of up to 42 days, a core period of 48 weeks and an extension period of up to 2 years to assess the efficacy, safety and pharmacokinetic (PK) of alpelisib in pediatric and adult participants with PROS.

Screening Period: Potential participants will be assessed for eligibility and undergo a whole body MRI scan to evaluate PROS-related lesions. Only those who meet all inclusion criteria will be eligible for randomization.

Core Period: Baseline is defined as the last available evaluation prior to the first dose of study treatment. Participants in Group 1 and Group 2 will be enrolled and treated with alpelisib in an open-label fashion.

* Group 1 (adults): will start with 250 mg once daily, with no dose escalation allowed. * Group 2 (children and adolescents): will start with 50 mg once daily for participants aged 2 to \<6 years, and 125 mg once daily for participants aged 6 to \<18 years.

Extension 1 Period: Participants in both groups will continue their treatment under the same rules as the core period. This period will last until Week 168 following the completion of the core period for each participant. Those who complete this period before the end of the study will transition to the Extension 2 period.

Extension 2 Period: Participants will continue their treatment under the same rules as the core and Extension 1 periods until the last participant completes the Extension 2 period. Participants still deriving clinical benefit from alpelisib at the end of the study may receive post-trial access (PTA) to alpelisib.

• Change from baseline (as assessed by BIRC) in target lesion volume [Срок оценки: Baseline, Week 12, Week 24, Week 48, Week 96, Week 144, Week 168, End of Treatment (last dose +< 14 day - Only for participants discontinuing on or prior to week 168)]
• Change from baseline (as assessed by BIRC) in MRI-measurable non-target lesion volume [Срок оценки: Baseline, Week 12, Week 24, Week 48, Week 96, Week 144, Week 168, End of Treatment (last dose +< 14 day - Only for participants discontinuing on or prior to week 168)]
• Change from baseline (as assessed by BIRC) in all MRI-measurable (target and non-target) lesion volume [Срок оценки: Baseline, Week 12, Week 24, Week 48, Week 96, Week 144, Week 168, End of Treatment (last dose +< 14 day - Only for participants discontinuing on or prior to week 168)]
• Change from baseline (as assessed by BIRC) in other non-target lesion [Срок оценки: Baseline, Week 12, Week 24, Week 48, Week 96, Week 144, Week 168, End of Treatment (last dose +< 14 day - Only for participants discontinuing on or prior to week 168)]
• Appearance of new lesions (as assessed by BIRC) [Срок оценки: Week 12, Week 24, Week 48, Week 96, Week 144, Week 168, End of Treatment (last dose +< 14 day - Only for participants discontinuing on or prior to week 168)]
• Proportion of participants with a radiological response [Срок оценки: Week 12, Week 24, Week 48, Week 96, Week 144, Week 168, End of Treatment (last dose +< 14 day - Only for participants discontinuing on or prior to week 168)]
• Duration of Response (DoR) [Срок оценки: From first documented response until progression of PROS lesions or death, assessed up to approximately 3 years]
• Alpelisib plasma concentration [Срок оценки: Week 1 Day 1 (Post-dose 3 hour), Week 4 Day 1 (Pre-dose and Post-dose 3 hour), Week 12 Day 1 (Pre-dose and Post-dose 3 hour)]
• Change from Baseline in Brief Pain Inventory (BPI) [Срок оценки: Baseline, Week 4, Week 8, Week 12, Week 16, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, End of Treatment (last dose +< 14 days)]
• Change from Baseline in Wong-Baker Faces Scale [Срок оценки: Baseline, Week 4, Week 8, Week 12, Week 16, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, End of Treatment (last dose +< 14 days)]
• Change from Baseline in Patient Global Impression of Symptom Severity (PGI-S) [Срок оценки: Baseline, Week 4, Week 8, Week 12, Week 16, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, End of Treatment (last dose +< 14 days)]
• Time to Treatment Failure (TTF) [Срок оценки: From Baseline up to approximately 3 years]