PIK3CA-Related Overgrowth Spectrum (PROS)Phase 2NCT06789913
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 (The ReInspire Study)
A Phase 2 study testing RLY-2608 in people with PIK3CA-Related Overgrowth Spectrum (PROS) and Lymphatic Malformations, run by Relay Therapeutics, Inc. at 40 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- PIK3CA-Related Overgrowth Spectrum (PROS), Lymphatic Malformations, Vascular Malformations
- What is being tested?
- RLY-2608
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 277 participants
- Where
- 40 sitesin 9 countries
- Study dates
- 13 Jun 2025to Oct 2031
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
- Systemic therapy or antibody within 5 half-lives of the therapy.
- Local therapy including radiation, surgery, or other procedures within 28 days; lesion(s) must have demonstrated progression after the procedure.
Trial locations and contacts
40 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
40 sites in 9 countries
United States22 sites, 22 recruiting
- Recruiting
Children's Hospital of Atlanta
Atlanta, Georgia, 30329
Lauren Rogers, 404-785-2727, Lauren.Rogers@choa.org
Gabrielle Dean, 404-785-8700, Gabrielle.Dean@choa.org
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Taizo Nakano, MD, 720-777-6663, taizo.nakano@childrenscolorado.org
- Recruiting
Johns Hopkins Medical Institute
Baltimore, Maryland, 21287
Alex Thompson, 410-955-5734, athomp43@jhmi.edu
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Vascular Anomalies Center, 617-355-5226, vascular@childrens.harvard.edu
- Recruiting
UNC Chapel Hill
Chapel Hill, North Carolina, 27599
Miriam Davis, 919-966-2333, miriam.davis@unc.edu
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Lexie Price, 513- 803-0226, Sarah.price@cchmc.org
- Recruiting
Cleveland Clinic Children's
Cleveland, Ohio, 44195
Ana Beatriz Ferreira Alves, 216-636-1926, ferreia2@ccf.org
- Recruiting
Corewell Health
Grand Rapids, Michigan, 49503
Amanda Bartolovic, Amanda.bartolovic@corewellhealth.org
- Recruiting
Texas Children's Hospital
Houston, Texas, 77030
Gaylon Stevenson, 832-824-1518, gnsteve1@texaschildrens.org
- Recruiting
Riley Children's Hospital
Indianapolis, Indiana, 46202
Riley PHOS Research Team, 317-948-8540, rileyphosresearchteam@iuhealth.org
- Recruiting
University of Iowa
Iowa City, Iowa, 52242
Maureen Austin, 319-356-0378, Maureen-Austin@uiowa.edu
- Recruiting
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
D'Ann Pierce, 501-364-4440, PierceCarolD@uams.edu
- Recruiting
University of California, Los Angeles
Los Angeles, California, 90095
Brianna Connors, 310-825-6708, bconnors@mednet.ucla.edu
- Recruiting
University of Wisconsin, Madison
Madison, Wisconsin, 53715
Department of Dermatology, info@clinicaltrials.wisc.edu
- Recruiting
NYU Langone Health
New York, New York, 10016
- Recruiting
Stanford University
Palo Alto, California, 94304
Ramrada Lekwuttikarn, 650-313-8207, ramrada1@stanford.edu
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Melissa Casey, 267-426-9188 ext. Option #4, caseyma@chop.edu
- Recruiting
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Chris Oless, 602-933-0188, dg_EDDT@phoenixchildrens.com
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
Mary Manyara, 507-266-3212, Manyara.mary@mayo.edu
- Recruiting
University of California, San Francisco
San Francisco, California, 94158
Beth Winger, MD, Beth.Winger@ucsf.edu
Audrey Hernando, (415) 502-2425, Audrey.Hernando@ucsf.edu
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98101
Whitney Eng, 206-884-4626, Whitney.Eng@seattlechildrens.org
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Allison Barnwell, pedshemonctrialreferral@wustl.edu
Australia5 sites, 5 recruiting
- Recruiting
Monash Health
Clayton, Victoria, 3168
Maurizio Pacilli, +613857283828, maurizio.pacilli@monash.edu
- Recruiting
Royal Melbourne Hospital
Parkville, Victoria, 3050
Dermatology Research, +61393424542, dermatologyresearch@mh.org.au
- Recruiting
Murdoch Children's Research Institute
Parkville, Victoria, 3052
Anthony Penington, +61393454545, Tony.Penington@rch.org.au
Trish Moreno, +61399366298, Trish.moreno@mcri.edu.au
- Recruiting
Sydney Children's Hospital, Randwick
Randwick, New South Wales, 2031
Sandra Montez, +610293821980, sandra.montez@health.nsw.gov.au
- Recruiting
Children's Health Queensland Hospital and Health
South Brisbane, Queensland, 4101
Melanie Jackson, +61730697631, oncology-research@health.qld.gov.au
Italy4 sites, 4 recruiting
- Recruiting
Ospedale Maggiore Policlinico
Milan, 20122
Dr. Riccardo Cavalli, 0255035355, riccardo.cavalli@policlinico.mi.it
- Recruiting
IRCCS Fondazione Policlinico Universitario A. Gemelli
Roma, 00168
Dr. Chiara Leoni, +39 06 3015 4584, chiara.leoni@policlinicogemelli.it
- Recruiting
Ospedale Pediatrico Bambino Gesù IRCCS
Roma
Andrea Diociaiuti, +390668592509, andrea.diociaiuti@opbg.net
- Recruiting
A.O.U Città della Salute e della Scienza di Torino
Torino
Dr. Alessandro Mussa, +390113135689, alessandro.mussa@unito.it
Spain3 sites, 3 recruiting
- Recruiting
Hospital Universitario A Coruña
A Coruña
Servicio Cirugía Pediátrica CHUAC, 34981178128, cirugia.infantil.chuac@sergas.es
- Recruiting
Hospital Sant Joan de Deu
Barcelona
Eulalia Baslega Torres, eulalia.baselga@sjd.es
Raquel Masip, raquel.masip@sjd.es
- Recruiting
Hospital Universitario La Paz
Madrid
Juan Carlos López Gutiérrez, +34917277019, juanc.lopez@salud.madrid.org
United Kingdom2 sites, 2 recruiting
- Recruiting
Chelsea and Westminster Hospital
London, SW10 9NH
Rhian Bull, +44 0203 3155295, Rhian.Bull@nhs.net
- Recruiting
Great Ormond Street Hospital for Children
London
Maanasa Polubothu, +4402074059200, maanasa.polubothu@gosh.nhs.uk
Belgium1 site, 1 recruiting
- Recruiting
UC Louvain
Ottignies-Louvain-la-Neuve
Emmanuel Seront, +3227649475, emmanuel.seront@saintluc.uclouvain.be
An Van Damme, +3227645106, an.vandamme@saintluc.uclouvain.be
Germany1 site, 1 recruiting
- Recruiting
University of Halle
Halle, Germany
Simone Hettmer, +493455572388, simone.hettmer@uk-halle.de
Ireland1 site, 1 recruiting
- Recruiting
Children's Health Ireland at Crumlin
Dublin, D12 N512
Breda Kane, 014096100, Breda.kane@childrenshealthireland.ie
About this study
Official title: 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
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, Klippel Trenaunay Syndrome
- Being tested
- RLY-2608, Placebo
- Medical subject headings
- Lymphatic Abnormalities, Vascular Malformations, Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi, Klippel-Trenaunay-Weber Syndrome, Megalencephaly cutis marmorata telangiectatica congenita
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RLY-2608Drug
RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.
PlaceboDrug
RLY-2608 matched-placebo
| Study group | Role | What they receive |
|---|---|---|
| Part 1, Group 1 | Experimental | RLY-2608 for patients ≥12 years old with PROS or malformations with PIK3CA mutation. Multiple doses of RLY-2608 for oral administration. Receives: Drug: RLY-2608 |
| Part 1, Group 2 | Experimental | 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. Receives: Drug: RLY-2608 |
| Part 1, Group 3 | Experimental | 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. Receives: Drug: RLY-2608 |
| Part 2, Group 1 | Experimental | 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. Receives: Drug: RLY-2608 |
| Part 2, Group 2 | Experimental | 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. Receives: Drug: RLY-2608 |
| Part 2, Group 3 | Experimental | 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. Receives: Drug: RLY-2608 |
| Part 3, Arm 1 | Experimental | 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. Receives: Drug: RLY-2608 |
| Part 3, Arm 2 | Placebo comparator | Adult (>18 yo) and pediatric (6 to <18 yo) participants with PROS and malformations with PIK3CA mutation will be randomized to receive placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parts 1 and 2: Determination of a recommended phase 2 dose RP2D(s) for Groups 1, 2, and 3
Measured: 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).
Measured: Cycle 1 of treatment and at the end of every cycle until study discontinuation
Part 3: Percentage of participants with volumetric Response.
Measured: Baseline, Week 24
Secondary outcomes (9)
Part 1 and 2: Percent change from baseline in lesion volume
Measured: Baseline, Week 24
Part 1 and 2: Duration of response, defined as the time of first documented response to the date of first documented disease progression or death due to any cause
Measured: Approximately every 3 months for approximately the first year, and then every 6 months during treatment
Part 1 and 2: Percentage of participants with volumetric response
Measured: Baseline, week 12, week 24
Part 1 and 2: Plasma concentrations and PK parameters of RLY-2608
Measured: Approximately every 2 weeks in Cycle 1, then again at Cycles 2, 4 and Cycle 7 depending on the participant's group
Part 1 and 2: PIK3CA mutational status in lesional fluid and/or tissue
Measured: Prior to enrollment
Part 3: Percentage of participants with improvement compared to baseline based on PGI-S, PGI-C and IGIC
Measured: Approximately once a month until end of treatment
Part 3: Change from baseline by age-appropriate PROMIS Profile
Measured: Approximately once a month until end of treatment
Part 3: Change from baseline in EQ-5D, EQ-5D-Y, or EQ-5D-Y Proxy
Measured: Approximately once a month until end of treatment
Part 3: Percent change from baseline in lesion volume
Measured: Approximately every 3 months for approximately the first year, and then every 6 months during treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2025
- Study start13 Jun 2025
- Primary completionJul 2031 (estimated)
- Study completionOct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PIK3CA-Related Overgrowth Spectrum (PROS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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 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 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.
- Masking
- None (open label)
- Enrolment
- 277 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Relay Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06789913
- Sponsor's protocol ID
- RLY-2608-201
- Other IDs
- 2024-518895-30-00
- Status last verified
- Jun 2026
- First submitted
- 17 Jan 2025
- Last updated
- 25 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No