Study Assessing Long-term Safety and Efficacy of Alpelisib in Patients With PIK3CA-Related Overgrowth Spectrum (PROS) Who Previously Participated in Study CBYL719F12002 (EPIK-P1)

A Phase II Study to Evaluate the Long-term Safety and Efficacy of Alpelisib in Patients With PIK3CA-Related Overgrowth Spectrum (PROS) Who Previously Participated in Study CBYL719F12002 (EPIK-P1)

This is a prospective interventional Phase II multi center study, open label, preceded by a retrospective non-interventional period, to assess the long-term safety and efficacy of alpelisib, in pediatric and adult participants with PROS.

The study will enroll males and females aged ≥2 years who previously participated in EPIK-P1 study and who continued to receive treatment with alpelisib after the cut-off date used in EPIK-P1 (NCT04285723).

The study has an initial retrospective period and a subsequent prospective period.

The retrospective period, is a non-interventional study period and will start one day after the EPIK-P1 data cut-off date (i.e. 10-Mar-2020). It will end the day before the first interventional dose of alpelisib is administered in the prospective period of this study (Day -1). Key safety and efficacy information that was previously collected as per local medical practice and recorded in the medical charts of eligible participants will be longitudinally abstracted.

The prospective period, is an interventional study period and will start on the day of the first interventional dose administration in the prospective period. It will end after all participants have completed at least 5 years of treatment in the prospective period of the study or discontinued earlier, whichever occurs earlier. During this study period, safety and efficacy data will be prospectively collected following a structured plan that is common to all participants.

Inclusion Criteria:

• Participants who had previously participated in the study EPIK-P1.
• Signed informed consent form and assent (when applicable) from the participant, parent, or guardian must be obtained prior to any study related screening procedures being performed.
• Participant is treated with at least one dose of alpelisib after the EPIK-P1 study data cut- off date of 09-Mar-2020.

Exclusion Criteria:

For participants in the retrospective period

- All EPIK-P1 participants who permanently discontinued the investigational drug on or prior to the cut-off date 09-Mar-2020.

For participants in the prospective period

• Previous alpelisib treatment discontinuation (after 09-Mar-2020) due to any of the following adverse events:

  • Grade 4 skin and subcutaneous tissue disorders
  • Stevens-Johnson-Syndrome (SJS)/ Toxic Epidermal Necrolysis (TEN) or other SJS/TEN-like severe skin reactions (any grade)
  • Grade 4 hyperglycemia without confounding factors
  • Pneumonitis (any grade)
  • Grade 4 stomatitis
  • Grade 4 pancreatitis
  • Recurrent grade 4 thrombocytopenia
  • Grade 3 or 4 serum creatinine increase
  • Grade 4 isolated total bilirubin elevation
  • Recurrent grade 3 or 4 QT interval corrected by Fridericia's formula prolongation (>500 ms or >60 ms change from baseline)

• Known impairment of GI function due to concomitant disease that may significantly alter the absorption of the study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) at time of informed consent.

• Participant with uncontrolled diabetes mellitus (Type I or II) at time of informed consent.

Other inclusion/exclusion criteria may apply