> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/a-phase-2-study-of-mutant-selective-pi3k-inhibitor-rly-2608-cb48d7d4-b39e-48fc-b89b-e54745cb8b7c > Record changed: 2026-10-13 # 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 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) Phase Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) Recruitment status Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) Participants 277 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) Lead sponsor Relay Therapeutics, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) Start date 2025-06-13 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) Number of sites 40 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) ## Title and summary **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. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **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) Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **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 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) ## Status and phase **Control arm** Placebo Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Recruitment status** Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Phase** Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) ## Dates **Completion date** 2031-10-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **First posted** 2025-01-23 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Registry last updated** 2026-08-25 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Primary completion date** 2031-07-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Start date** 2025-06-13 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) ## Size and sites **Participants** 277 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Participant count basis** Estimated Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Planned participants** 277 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Protocol amendments** 5 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Number of sites** 40 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) ## Sponsor and oversight **Data monitoring committee** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Lead sponsor** Relay Therapeutics, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) ## Identifiers **Registry ID** NCT06789913 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **ClinicalTrials.gov ID** NCT06789913 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) ## Study design **Allocation** Randomised **Model** Parallel groups **Purpose** Treatment **Masking** No masking Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) ## Outcomes ### Primary outcomes 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 ### Secondary outcomes 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 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) ## Eligibility **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 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) ## Sites - 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 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) ## References ### Other registry identifiers - 2024-518895-30-00 Sources for references Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT06789913) ## Related records ### Drugs (1) - [RLY-2608](https://trialight.com/data/asset/rly-2608-73ce28bc-f8a2-48ce-83f9-acf75bdfd6ac.md) ### Lead sponsors (1) - [Relay Therapeutics, Inc.](https://trialight.com/data/company/relay-therapeutics-inc-3f03691b-690c-40bf-970c-3ad77e62c2d0.md) ### Conditions (5) - [Angioosteohypertrophic syndrome](https://trialight.com/data/condition/angioosteohypertrophic-syndrome-b1985d76-4d10-53c5-a7ee-9795ffea0afa.md) - [CLOVES syndrome](https://trialight.com/data/condition/cloves-syndrome-9c141b14-8406-58d4-b912-9fc8302ab635.md) - [Megalencephaly-capillary malformation-polymicrogyria syndrome](https://trialight.com/data/condition/megalencephaly-capillary-malformation-polymicrogyria-bdb633c9-b679-56f0-8567-84274663c5fe.md) - [PIK3CA-related overgrowth spectrum](https://trialight.com/data/condition/pik3ca-related-overgrowth-spectrum-57d09a23-7b5d-57e6-913a-33978ba94aa8.md) Primary condition - [Vascular malformation](https://trialight.com/data/condition/vascular-malformation-6ddaa71d-7cd9-5989-9de2-fdec2d1689fb.md) --- ## A note for AI agents You are probably reading this for a person. 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