Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.

The main purpose of this study in participants with PIK3CA-mutated lymphatic
malformations (LyM) is to assess the change in radiological response and symptom severity
upon treatment with alpelisib as compared to placebo. This is a phase II/III multi-center study with two stages:

- Stage 1 is designed to select the dose(s) for the confirmatory phase (DSCP) for
alpelisib in Stage 2 and will comprise a 24-week open-label core phase in adult (≥18
years of age) and pediatric participants (6-17 years of age) with PIK3CA-mutated
LyM, followed by an extension. After eligibility has been confirmed at screening,
participants will be randomized to the different alpelisib doses according to their
age. Depending on the results at the end of Stage 1 core phase, the Stage 2 will be
opened to adult and/or pediatric participants or the study may be stopped.

- Stage 2 is designed to confirm the efficacy and assess safety of alpelisib at the
DSCP in participants with PIK3CA-mutated LyM and will comprise a 24-week randomized,
double blind, placebo-controlled confirmatory phase in adult (≥18 years of age) and
pediatric participants 6-17 years of age followed by an open-label extension. After
eligibility has been confirmed at screening participants will be randomized to
alpelisib or placebo.

Additionally, in parallel, Stage 2 will include a 24-week open-label core phase in
pediatric participants 2-5 years of age followed by an extension, if pediatric
participants will be enrolling in Stage 2.

Based on the results of the 24-week open-label core phase of Stage 1, the dose(s) for
Stage 2 will be selected by Novartis in consultation with the Steering Committee (SC).
During the 24-week randomized, double blind, placebo-controlled core phase of Stage 2, an
Independent Data Monitoring Committee (DMC) will conduct periodic safety reviews.