RLY-2608-201-Ph2 Study of RLY-2608 in PROS and PIK3CA Driven Malformations

Phase 2

Not yet recruiting

• Conditions: PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation

• Registration Number: 2024-518895-30-00
• Lead Sponsor: Relay Therapeutics Inc.

Brief Summary

Parts 1 and 2

- To determine the RP2D(s) for Groups 1, 2, and 3

- To determine the safety and tolerability of RLY-2608

Part 3

- To determine the efficacy of RLY-2608 compared to placebo in participants as assessed by volumetric response rate

Detailed Description

Not available

Study Timeline

• Study First Posted: 2025-05-14
• Last Update Posted: 2025-05-20

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 22

Inclusion Criteria

Lansky (<16 yo) or Karnofsky (≥16 yo) performance status of ≥50.

The participant must have a clinical diagnosis of PROS or a malformation within the ISSVA 2018 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

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

Received disease-directed therapy prior to first dose of study drug

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Parts 1 and 2: RP2D(s) for Groups 1, 2, and 3		Parts 1 and 2: RP2D(s) for Groups 1, 2, and 3
Parts 1 and 2: Overall safety profile of RLY-2608 as assessed by the type, frequency, severity, timing, and relationship to RLY-2608 of any DLT, AEs, serious adverse events (SAEs), changes in vital signs, ECGs, and safety laboratory tests		Parts 1 and 2: Overall safety profile of RLY-2608 as assessed by the type, frequency, severity, timing, and relationship to RLY-2608 of any DLT, AEs, serious adverse events (SAEs), changes in vital signs, ECGs, and safety laboratory tests
Part 3: Percentage of participants with volumetric response		Part 3: Percentage of participants with volumetric response

Secondary Outcome Measures

Name	Time	Method
Parts 1 and 2: Percentage of participants with volumetric response		Parts 1 and 2: Percentage of participants with volumetric response
Parts 1 and 2: Percent change from baseline in lesion volume by blinded independent central review (BICR)		Parts 1 and 2: Percent change from baseline in lesion volume by blinded independent central review (BICR)
Parts 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		Parts 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
Parts 1 and 2: Plasma concentrations and PK parameters, including area under the concentration-time curve (AUC), Cmax, tmax, terminal half-life (t1/2), total body clearance following oral dose (CL/F), and other relevant PK parameters for RLY-2608		Parts 1 and 2: Plasma concentrations and PK parameters, including area under the concentration-time curve (AUC), Cmax, tmax, terminal half-life (t1/2), total body clearance following oral dose (CL/F), and other relevant PK parameters for RLY-2608
Part 3: Percentage of participants compared to baseline based on PGI-S, PGI-C and IGIC of RLY-2608 compared to placebo		Part 3: Percentage of participants compared to baseline based on PGI-S, PGI-C and IGIC of RLY-2608 compared to placebo
Part 3: Change from baseline by age-appropriate PROMIS Profile (PROMIS-29 Profile v2.1, PROMIS Pediatric-25 Profile GenPop v3.0, and/or PROMIS Parent-Proxy-25 Profile GenPop v3.0		Part 3: Change from baseline by age-appropriate PROMIS Profile (PROMIS-29 Profile v2.1, PROMIS Pediatric-25 Profile GenPop v3.0, and/or PROMIS Parent-Proxy-25 Profile GenPop v3.0
Part 3: Change from baseline in EQ-5D-5L, EQ-5D-Y-3L, or EQ-5D-Y-3L Proxy 1		Part 3: Change from baseline in EQ-5D-5L, EQ-5D-Y-3L, or EQ-5D-Y-3L Proxy 1
Part 3: Percent change from baseline in lesion volume by BICR		Part 3: Percent change from baseline in lesion volume by BICR
Part 3: Duration of response, defined as the time of first documented response by BICR to the date of first documented disease progression or death due to any cause		Part 3: Duration of response, defined as the time of first documented response by BICR to the date of first documented disease progression or death due to any cause
Part 3: Overall safety profile of RLY-2608 as a single agent as assessed by the type, frequency, severity, timing, and relationship to RLY-2608 of any DLT; AE; SAE; or change in vital signs, ECGs, and safety laboratory test		Part 3: Overall safety profile of RLY-2608 as a single agent as assessed by the type, frequency, severity, timing, and relationship to RLY-2608 of any DLT; AE; SAE; or change in vital signs, ECGs, and safety laboratory test

Trial Locations

Locations (4)

Cliniques Universitaires Saint-Luc; 🇧🇪 Sint-Lambrechts-Woluwe, Belgium

Ospedale Pediatrico Bambino Gesu; 🇮🇹 Rome, Italy

Hospital Sant Joan De Deu Barcelona; 🇪🇸 Esplugues De Llobregat, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Cliniques Universitaires Saint-Luc

🇧🇪Sint-Lambrechts-Woluwe, Belgium

Emmanuel Seront

Site contact

3227645106

emmanuel.seront@saintluc.uclouvain.be