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

NCT ID: NCT06789913

Last Updated: 2026-01-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

277 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-13

Study Completion Date

2031-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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PIK3CA-Related Overgrowth Spectrum (PROS) Lymphatic Malformations Vascular Malformations PIK3CA Mutation CLOVES Syndrome Klippel Trenaunay Syndrome Megalencephaly-capillary Malformation Polymicrogyria Syndrome (MCAP)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Part 1: Dose selection: Participants ≥12 years old with PROS or malformations with PIK3CA mutation (Group 1) will be randomly assigned to a selected dose of RLY-2608 in an open-label fashion, stratified based on prior treatment with alpelisib. Groups 2 (6 to \<12 years old) and 3 (2 to \<6 years old): RLY-2608 will be studied in pediatric participants in a dose escalation design.

Part 2: Part 2 will explore the clinical activity of RLY-2608 at 1 or more adult, adolescent, and pediatric recommended Phase 2 dose (RP2D) in various populations of participants with PROS and malformations associated with PIK3CA mutations in an open-label basket trial design.

Part 3: In Part 3, adult (\>18 yo), and adolescent and pediatric (6 to \<18 yo) participants with PROS and malformations with PIK3CA mutation will be randomized to receive RLY-2608 at the Group 1 and 2 RP2Ds versus placebo. Randomization will be stratified based on indication, and prior systemic therapy.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1, Group 1

RLY-2608 for patients ≥12 years old with PROS or malformations with PIK3CA mutation. Multiple doses of RLY-2608 for oral administration.

Group Type EXPERIMENTAL

RLY-2608

Intervention Type DRUG

RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.

Part 1, Group 2

RLY-2608 for participants 6 to \<12 years old with PROS or malformations with PIK3CA mutation.

RLY-2608 will be studied in pediatric participants in a dose escalation design.

Group Type EXPERIMENTAL

RLY-2608

Intervention Type DRUG

RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.

Part 1, Group 3

Part 1, Group 3: RLY-2608 for participants 2 to \<6 years old with PROS or malformations with PIK3CA mutation.

RLY-2608 will be studied in pediatric participants in a dose escalation design.

Group Type EXPERIMENTAL

RLY-2608

Intervention Type DRUG

RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.

Part 2, Group 1

Dose expansion single-arm cohorts for various subpopulations of participants ≥12 years old with PROS or malformations with PIK3CA mutation.

Oral dose of RLY-2608 as determined during Part 1.

Group Type EXPERIMENTAL

RLY-2608

Intervention Type DRUG

RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.

Part 2, Group 2

Dose expansion cohorts for participants 6 to \<12 years old with PROS or malformations with PIK3CA mutation.

Oral dose of RLY-2608 as determined during Part 1.

Group Type EXPERIMENTAL

RLY-2608

Intervention Type DRUG

RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.

Part 2, Group 3

Dose expansion cohorts for participants 2 to \<6 years old with PROS or malformations with PIK3CA mutation.

Oral dose of RLY-2608 as determined during Part 1.

Group Type EXPERIMENTAL

RLY-2608

Intervention Type DRUG

RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.

Part 3, Arm 1

Adult (\>18 yo), and adolescent and pediatric (6 to \<18 yo) participants with PROS and malformations with PIK3CA mutation will be randomized to receive RLY-2608 at oral dose determined during Part 1/2 versus placebo.

Group Type EXPERIMENTAL

RLY-2608

Intervention Type DRUG

RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.

Part 3, Arm 2

Adult (\>18 yo), and adolescent and pediatric (6 to \<18 yo) participants with PROS and malformations with PIK3CA mutation will be randomized to receive placebo.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

RLY-2608 matched-placebo

Interventions

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RLY-2608

RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.

Intervention Type DRUG

Placebo

RLY-2608 matched-placebo

Intervention Type DRUG

Eligibility Criteria

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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.

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:

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

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Relay Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status RECRUITING

University of California, Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

Stanford University

Palo Alto, California, United States

Site Status RECRUITING

University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Children's Hospital of Atlanta

Atlanta, Georgia, United States

Site Status RECRUITING

Riley Children's Hospital

Indianapolis, Indiana, United States

Site Status RECRUITING

Johns Hopkins Medical Institute

Baltimore, Maryland, United States

Site Status RECRUITING

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

UNC Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

Cleveland Clinic Children's

Cleveland, Ohio, United States

Site Status RECRUITING

Texas Children's Hospital

Houston, Texas, United States

Site Status RECRUITING

University of Wisconsin, Madison

Madison, Wisconsin, United States

Site Status RECRUITING

Sydney Children's Hospital, Randwick

Randwick, New South Wales, Australia

Site Status RECRUITING

Monash Health

Clayton, Victoria, Australia

Site Status RECRUITING

Murdoch Children's Research Institute

Parkville, Victoria, Australia

Site Status RECRUITING

UC Louvain

Ottignies-Louvain-la-Neuve, , Belgium

Site Status RECRUITING

Ospedale Pediatrico Bambino Gesù IRCCS

Roma, , Italy

Site Status RECRUITING

Hospital Sant Joan de Deu

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, , Spain

Site Status RECRUITING

Great Ormond Street Hospital for Children

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Belgium Italy Spain United Kingdom

Central Contacts

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Relay Therapeutics, Inc

Role: CONTACT

617-322-0731

Facility Contacts

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Chris Oless

Role: primary

602-933-0188

D'Ann Pierce

Role: primary

501-364-4440

Mikayla Henderson

Role: primary

310-825-6708

Ramrada Lekwuttikarn

Role: primary

650-313-8207

Beth Winger, MD

Role: primary

Audrey Hernando

Role: backup

(415) 502-2425

Taizo Nakano, MD

Role: primary

720-777-6663

Lauren Rogers

Role: primary

404-785-2727

Gabrielle Dean

Role: backup

404-785-8700

Riley PHOS Research Team

Role: primary

317-948-8540

Alex Thompson

Role: primary

410-955-5734

Relay Therapeutics

Role: primary

617-322-0731

Mary Manyara

Role: primary

507-266-3212

Allison Barnwell

Role: primary

Miriam Davis

Role: primary

919-966-2333

Lexie Price

Role: primary

513- 803-0226

Janet Choe

Role: primary

216-636-3398

Ana Beatriz Ferreira Alves

Role: backup

216-636-1926

Gaylon Stevenson

Role: primary

832-824-1518

Role: primary

Other Identifiers

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2024-518895-30-00

Identifier Type: CTIS

Identifier Source: secondary_id

RLY-2608-201

Identifier Type: -

Identifier Source: org_study_id

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