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)

NCT06997588 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CBYL719F122022024-519960-42-00
• Study Type: interventional
• Target: 104
• Locations: 9 countries
• Sites: 28

Brief Summary

This study is designed to demonstrate the efficacy and assess safety and tolerability of oral daily alpelisib in participants with PIK3CA-related overgrowth spectrum (PROS).

Conditions

PIK3CA-related Overgrowth Spectrum (PROS)

Keywords

PIK3CA-related overgrowth spectrum (PROS); Alpelisib (BYL719); Phase II; Adult; Pediatric; Adolescent

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with a confirmed objective response by BIRC

  Confirmed objective response is defined as achieving radiological response, confirmed by a subsequent assessment performed at least after 4 weeks. The achievement of radiological response requires ≥20% reduction from baseline in the sum of target lesion volumes (1 to 3 target lesions, assessed by Magnetic Resonance Imaging (MRI) by a blinded independent review committee (BIRC)), provided that none of the individual target lesions has ≥20% increase from nadir, and in absence of progression of non-target lesions and without new lesions.

  Up to Week 48

Secondary Outcomes (17)

• Change from baseline (as assessed by BIRC) in target lesion volume

  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

  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

  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

  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)

  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)

Study Arms (2)

Group 1

EXPERIMENTAL

Adult participants ≥18 years of age.

Drug: Alpelisib

Group 2

EXPERIMENTAL

Children and adolescents 2 to \<18 years of age.

Drug: Alpelisib

Interventions

Alpelisib DRUG

Oral Film-Coated Tablet (FCT): * Group 1: 250 mg once daily * Group 2, 6 to \<18 years: 125 mg once daily (starting dose) Granules: • Group 2, 2 to \<6 years: 50 mg once daily (starting dose)

Also known as: BYL719

Group 1; Group 2

Eligibility Criteria

• Age: 2 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants aged ≥2 years at the time of informed consent/assent.
• Participants with diagnosis of PROS (according to Clinical Diagnostic Criteria for PROS proposed by Keppler Noreuil et al 2014) with symptomatic AND progressive overgrowth, who have syndromic disease or isolated features (with the exception of isolated macrodactyly, macrocephaly or epidermal nevus) at the time of informed consent/assent.
• Documented evidence of a somatic mutation(s) in the PIK3CA gene performed in local laboratories using a DNA-based test AND available archival tissue (if archival tissue sample is not available, a fresh biopsy should be performed, if it is not clinically contraindicated) at the time of informed consent/assent.
• Karnofsky (in participants \>16 years of age at study entry) or Lansky (≤16 years of age at study entry) performance status index ≥50.
• PGI-S score of mild, moderate, severe, or very severe at screening.
• Adequate bone marrow and organ function.
• Presence of at least 1 PROS-related measurable lesion (longest diameter ≥2 cm) confirmed by BIRC assessment and associated with complaints, clinical symptoms or functional limitations affecting the participant's everyday life.

You may not qualify if:

• Participant with only isolated macrodactyly, epidermal nevus/nevi and macroencephaly (the only clinical feature or a combination of any of three of them), in absence of other PROS-related lesions at the time of informed consent/assent.
• Previous treatment with alpelisib and/or any other phosphatidylinositol 3-kinase (PI3K) inhibitor(s) (except treatment attempt, defined as the attempt to treat PROS with any of PI3K inhibitors, with treatment duration less than 2 weeks and stopped at least 4 weeks prior to the first dose of study medication with alpelisib).
• Debulking or other major surgery performed within 3 months at the time of informed consent/assent.
• Radiation exposure for PROS treatment purpose within 12 months prior to informed consent/assent.
• Clinically meaningful PROS-related thrombotic event (Grade 2 and more as per CTCAE v4.03) within 30 days before informed consent/assent, and/or sclerotherapy/embolization for vascular complications performed within 6 weeks before informed consent/assent.
• Clinically meaningful bleeding from PROS-related lesion (Grade 2 and more as per CTCAE v4.03) within 30 days before study treatment initiation.
• Participants with clinically significant worsening of PROS-related laboratory abnormalities, physical signs and symptoms (such as, but not limited to increase of D-dimers, worsening of underlying pain, newly occurring swelling or redness) indicating an uncontrolled condition during the screening phase.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (30)

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Cinn Children Hosp Medical Center

Cincinnati, Ohio, 45206, United States

RECRUITING

Novartis Investigative Site

Sydney, New South Wales, 2010, Australia

RECRUITING

Novartis Investigative Site

Sydney, New South Wales, 2031, Australia

RECRUITING

Novartis Investigative Site

North Adelaide, South Australia, 5066, Australia

RECRUITING

Novartis Investigative Site

Salzburg, 5020, Austria

RECRUITING

Novartis Investigative Site

Vienna, A 1090, Austria

RECRUITING

Novartis Investigative Site

Ghent, 9000, Belgium

RECRUITING

Novartis Investigative Site

Angers, 49933, France

RECRUITING

Novartis Investigative Site

Bron, 69677, France

RECRUITING

Novartis Investigative Site

Dijon, 21000, France

RECRUITING

Novartis Investigative Site

Montpellier, 34295, France

RECRUITING

Novartis Investigative Site

Paris, 75015, France

RECRUITING

Novartis Investigative Site

Toulouse, 31400, France

RECRUITING

Novartis Investigative Site

Tours, 37044, France

RECRUITING

Novartis Investigative Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

RECRUITING

Novartis Investigative Site

Düsseldorf, North Rhine-Westphalia, 40225, Germany

RECRUITING

Novartis Investigative Site

Leipzig, Saxony, 04103, Germany

RECRUITING

Novartis Investigative Site

Halle, Saxony-Anhalt, 06120, Germany

RECRUITING

Novartis Investigative Site

Berlin, 13353, Germany

RECRUITING

Novartis Investigative Site

Stuttgart, 70374, Germany

RECRUITING

Novartis Investigative Site

Roma, RM, 00168, Italy

RECRUITING

Novartis Investigative Site

Torino, TO, 10126, Italy

RECRUITING

Novartis Investigative Site

Trieste, TS, 34137, Italy

RECRUITING

Novartis Investigative Site

Esplugues, Barcelona, 08950, Spain

RECRUITING

Novartis Investigative Site

A Coruña, 15006, Spain

RECRUITING

Novartis Investigative Site

Barcelona, 08035, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28046, Spain

RECRUITING

Novartis Investigative Site

Lausanne, 1011, Switzerland

RECRUITING

Novartis Investigative Site

Liverpool, L12 2AP, United Kingdom

RECRUITING

MeSH Terms

Interventions

Alpelisib

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: May 30, 2025
• Study Start: October 9, 2025
• Primary Completion (Estimated): August 2, 2028
• Study Completion (Estimated): September 30, 2030
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (2); GB (1); ES (4); CH (1); FR (7); BE (1); AU (3); DE (6); IT (3)