Recruiting

Phase 2

RLY-2608A 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 (The ReInspire Study)

Sponsor:

Relay Therapeutics, Inc.

Code:

NCT06789913

Conditions

PIK3CA-Related Overgrowth Spectrum (PROS)

Lymphatic Malformations

Vascular Malformations

PIK3CA Mutation

CLOVES Syndrome

Eligibility Criteria

Sex: All

Age: 2+

Healthy Volunteers: Not accepted

Interventions

RLY-2608

Placebo

Study Details

Brief summary:

This is a 3-part Phase 2 randomized study evaluating the safety and efficacy of the mutant-selective PI3Kα inhibitor, zovegalisib (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.

Conditions

PIK3CA-Related Overgrowth Spectrum (PROS)

Lymphatic Malformations

Vascular Malformations

PIK3CA Mutation

CLOVES Syndrome

Study ID

NCT06789913

Start date

Jun 13, 2025

Status verified date

Jun, 2026

Completion date

Oct, 2031

Anticipated

Primary completion date

Jul, 2031

Anticipated

Eligibility Criteria

Sex: All

Age: 2+

Healthy Volunteers: Not accepted

Key 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, with the sponsor's approval, 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.

Key Exclusion Criteria:

Known hypersensitivity to RLY-2608.
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.

Study Design

Enrollment

277 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

experimental: Part 3, Arm 1

Adult (>18 yo) 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.

placebo comparator: Part 3, Arm 2

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

Interventions

RLY-2608

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

Placebo

RLY-2608 matched-placebo

Primary outcome measure

Parts 1 and 2: Determination of a recommended phase 2 dose RP2D(s) for Groups 1, 2, and 3 [ Time Frame: Cycle 1 of treatment and at the end of every cycle until study discontinuation ]
Parts 1 and 2: Occurrence/frequency of Adverse Events (AEs), changes in vital signs, ECGs, and safety laboratory tests and their relationship to the study drugs (safety and tolerability). [ Time Frame: Cycle 1 of treatment and at the end of every cycle until study discontinuation ]
Part 3: Percentage of participants with volumetric Response. [ Time Frame: Baseline, Week 24 ]

Central Contacts and Locations

Central contacts

Relay Therapeutics, Inc

617-322-0731 ClinicalTrials@relaytx.com

Locations

Phoenix Children's Hospital

Recruiting

Phoenix, Arizona, United States, 85016

Contacts

Chris Oless

602-933-0188 dg_EDDT@phoenixchildrens.com

Arkansas Children's Hospital

Recruiting

Little Rock, Arkansas, United States, 72202

Contacts

D'Ann Pierce

501-364-4440 PierceCarolD@uams.edu

University of California, Los Angeles

Recruiting

Los Angeles, California, United States, 90095

Contacts

Brianna Connors

310-825-6708 bconnors@mednet.ucla.edu

Stanford University

Recruiting

Palo Alto, California, United States, 94304

Contacts

Ramrada Lekwuttikarn

650-313-8207 ramrada1@stanford.edu

University of California, San Francisco

Recruiting

San Francisco, California, United States, 94158

Contacts

Beth Winger, MD

Beth.Winger@ucsf.edu

Audrey Hernando

(415) 502-2425 Audrey.Hernando@ucsf.edu

Children's Hospital Colorado

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Taizo Nakano, MD

720-777-6663 taizo.nakano@childrenscolorado.org

Children's Hospital of Atlanta

Recruiting

Atlanta, Georgia, United States, 30329

Contacts

Lauren Rogers

404-785-2727 Lauren.Rogers@choa.org

Gabrielle Dean

404-785-8700 Gabrielle.Dean@choa.org

Riley Children's Hospital

Recruiting

Indianapolis, Indiana, United States, 46202

Contacts

Riley PHOS Research Team

317-948-8540 rileyphosresearchteam@iuhealth.org

University of Iowa

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Maureen Austin

319-356-0378 Maureen-Austin@uiowa.edu

Johns Hopkins Medical Institute

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Alex Thompson

410-955-5734 athomp43@jhmi.edu

Boston Children's Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Vascular Anomalies Center

617-355-5226 vascular@childrens.harvard.edu

Corewell Health

Recruiting

Grand Rapids, Michigan, United States, 49503

Contacts

Amanda Bartolovic

Amanda.bartolovic@corewellhealth.org

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Mary Manyara

507-266-3212 Manyara.mary@mayo.edu

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Allison Barnwell

pedshemonctrialreferral@wustl.edu

NYU Langone Health

Recruiting

New York, New York, United States, 10016

UNC Chapel Hill

Recruiting

Chapel Hill, North Carolina, United States, 27599

Contacts

Miriam Davis

919-966-2333 miriam.davis@unc.edu

Cincinnati Children's Hospital Medical Center

Recruiting

Cincinnati, Ohio, United States, 45229

Contacts

Lexie Price

513- 803-0226 Sarah.price@cchmc.org

Cleveland Clinic Children's

Recruiting

Cleveland, Ohio, United States, 44195

Contacts

Ana Beatriz Ferreira Alves

216-636-1926 ferreia2@ccf.org

Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Melissa Casey

267-426-9188 caseyma@chop.edu

Texas Children's Hospital

Recruiting

Houston, Texas, United States, 77030

Contacts

Gaylon Stevenson

832-824-1518 gnsteve1@texaschildrens.org

Seattle Children's Hospital

Recruiting

Seattle, Washington, United States, 98101

Contacts

Whitney Eng

206-884-4626 Whitney.Eng@seattlechildrens.org

University of Wisconsin, Madison

Recruiting

Madison, Wisconsin, United States, 53715

Contacts

Department of Dermatology

info@clinicaltrials.wisc.edu

More Information

Sponsor

Relay Therapeutics, Inc.

Last update posted

Aug 25, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Relay Therapeutics, Inc. on 2026-08-25.