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)

NCT06789913
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Phase
Phase 2
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Recruitment status
Recruiting
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Participants
277
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Lead sponsor
Relay Therapeutics, Inc.
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Start date
2025-06-13
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Number of sites
40
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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.
clinicaltrials.gov
Short 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 (The ReInspire Study)
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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
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Control arm
Placebo
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 2
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Study type
Interventional
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Completion date
2031-10-01
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First posted
2025-01-23
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Registry last updated
2026-08-25
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Primary completion date
2031-07-01
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Start date
2025-06-13
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Participants
277
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Participant count basis
Estimated
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Planned participants
277
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Protocol amendments
5
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Number of sites
40
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Relay Therapeutics, Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06789913
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ClinicalTrials.gov ID
NCT06789913
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Parts 1 and 2: Determination of a recommended phase 2 dose RP2D(s) for Groups 1, 2, and 3

    Timeframe: Cycle 1 of treatment and at the end of every cycle until study discontinuation

  2. 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).

    Timeframe: Cycle 1 of treatment and at the end of every cycle until study discontinuation

  3. Part 3: Percentage of participants with volumetric Response.

    Timeframe: Baseline, Week 24

  1. Part 1 and 2: Percent change from baseline in lesion volume

    Timeframe: Baseline, Week 24

  2. 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

    Timeframe: Approximately every 3 months for approximately the first year, and then every 6 months during treatment

  3. Part 1 and 2: Percentage of participants with volumetric response

    Timeframe: Baseline, week 12, week 24

  4. Part 1 and 2: Plasma concentrations and PK parameters of RLY-2608

    Timeframe: Approximately every 2 weeks in Cycle 1, then again at Cycles 2, 4 and Cycle 7 depending on the participant's group

  5. Part 1 and 2: PIK3CA mutational status in lesional fluid and/or tissue

    Timeframe: Prior to enrollment

  6. Part 3: Percentage of participants with improvement compared to baseline based on PGI-S, PGI-C and IGIC

    Timeframe: Approximately once a month until end of treatment

  7. Part 3: Change from baseline by age-appropriate PROMIS Profile

    Timeframe: Approximately once a month until end of treatment

  8. Part 3: Change from baseline in EQ-5D, EQ-5D-Y, or EQ-5D-Y Proxy

    Timeframe: Approximately once a month until end of treatment

  9. Part 3: Percent change from baseline in lesion volume

    Timeframe: Approximately every 3 months for approximately the first year, and then every 6 months during treatment

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Children, Adults, Older adults
Minimum age
2 Years
Healthy volunteers
No

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.
Sources for eligibility
clinicaltrials.gov

  • Phoenix Children's HospitalPhoenix, United StatesRecruiting
  • Arkansas Children's HospitalLittle Rock, United StatesRecruiting
  • University of California, Los AngelesLos Angeles, United StatesRecruiting
  • Stanford UniversityPalo Alto, United StatesRecruiting
  • University of California, San FranciscoSan Francisco, United StatesRecruiting
  • Children's Hospital ColoradoAurora, United StatesRecruiting
  • Children's Hospital of AtlantaAtlanta, United StatesRecruiting
  • Riley Children's HospitalIndianapolis, United StatesRecruiting
  • University of IowaIowa City, United StatesRecruiting
  • Johns Hopkins Medical InstituteBaltimore, United StatesRecruiting
  • Boston Children's HospitalBoston, United StatesRecruiting
  • Corewell HealthGrand Rapids, United StatesRecruiting
  • Mayo ClinicRochester, United StatesRecruiting
  • Washington University School of MedicineSt Louis, United StatesRecruiting
  • NYU Langone HealthNew York, United StatesRecruiting
  • UNC Chapel HillChapel Hill, United StatesRecruiting
  • Cincinnati Children's Hospital Medical CenterCincinnati, United StatesRecruiting
  • Cleveland Clinic Children'sCleveland, United StatesRecruiting
  • Children's Hospital of PhiladelphiaPhiladelphia, United StatesRecruiting
  • Texas Children's HospitalHouston, United StatesRecruiting
  • Seattle Children's HospitalSeattle, United StatesRecruiting
  • University of Wisconsin, MadisonMadison, United StatesRecruiting
  • Sydney Children's Hospital, RandwickRandwick, AustraliaRecruiting
  • Children's Health Queensland Hospital and HealthSouth Brisbane, AustraliaRecruiting
  • Monash HealthClayton, AustraliaRecruiting

And 15 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2024-518895-30-00
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (5)