RLY-2608 for PIK3CA-related overgrowth spectrum (PROS) | PIK3CA-driven malformations

Inclusion criteria

• {"criterion_text":"- Lansky (<16 yo) or Karnofsky (≥16 yo) performance status of ≥50.\n- The participant must have a clinical diagnosis of PROS or a malformation within the ISSVA classifications\n- 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\n- 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

• {"criterion_text":"- Received disease-directed therapy prior to first dose of study drug (systemic therapy 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).\n- History of hypersensitivity to PI3K inhibitors.\n- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events\n- Clinically significant, uncontrolled cardiovascular disease"}

Primary endpoints

• {"endpoint_text":"- Parts 1 and 2: RP2D(s) for Groups 1, 2, and 3","definition_or_measurement_approach":"Determine recommended phase 2 dose(s) (RP2D) for Groups 1, 2, and 3 (dose-escalation/dose-finding endpoints for Parts 1 and 2)."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Safety and tolerability assessed by recording dose-limiting toxicities (DLTs), adverse events (AEs), serious adverse events (SAEs), and changes in vital signs, ECGs and safety laboratory tests (type, frequency, severity, timing, relationship to study drug)."}
• {"endpoint_text":"- Part 3: Percentage of participants with volumetric response at Week 24","definition_or_measurement_approach":"Proportion of participants achieving a volumetric response at Week 24 (measurement approach not specified in the primary endpoint statement)."}

Secondary endpoints

• {"endpoint_text":"- Parts 1 and 2: Percentage of participants with volumetric response at Weeks 12 and 24","definition_or_measurement_approach":"Proportion of participants with volumetric response assessed at Weeks 12 and 24."}
• {"endpoint_text":"- Parts 1 and 2: Percent change from baseline in lesion volume by blinded independent central review (BICR)","definition_or_measurement_approach":"Percent change from baseline in lesion volume as measured by blinded independent central review (BICR)."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Duration of response = time from first documented response to first documented disease progression or death from any cause."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Pharmacokinetic parameters including AUC, Cmax, tmax, t1/2, CL/F and other relevant PK measures following oral dosing."}
• {"endpoint_text":"- Part 3: Percentage of participants with improvement compared to baseline based on PGI-S, PGI-C and IGIC of RLY-2608 compared to placebo","definition_or_measurement_approach":"Proportion of participants with improvement versus baseline on patient/global impression scales (PGI-S, PGI-C, IGIC) comparing RLY-2608 to placebo."}
• {"endpoint_text":"- Part 3: Change from baseline by age-appropriate PROMIS Profile","definition_or_measurement_approach":"Change from baseline in age-appropriate PROMIS Profile scores."}
• {"endpoint_text":"- Part 3: Change from baseline in EQ-5D, EQ-5D-Y, or EQ-5D-Y Proxy","definition_or_measurement_approach":"Change from baseline in quality-of-life measured by EQ-5D instruments (EQ-5D, EQ-5D-Y or EQ-5D-Y Proxy)."}
• {"endpoint_text":"- Part 3: Percent change from baseline in lesion volume by BICR","definition_or_measurement_approach":"Percent change from baseline in lesion volume assessed by blinded independent central review (BICR)."}
• {"endpoint_text":"- Part 3: Duration of response, defined as the time of first documented response to the date of first documented disease progression by BICR or death due to any cause","definition_or_measurement_approach":"Duration of response per BICR = time from first documented response to first documented disease progression by BICR or death from any cause."}
• {"endpoint_text":"- Part 3: Overall safety profile of RLY-2608 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","definition_or_measurement_approach":"Overall safety and tolerability assessed by recording DLTs, AEs, SAEs, and changes in vital signs, ECGs, and safety laboratory tests (type, frequency, severity, timing, relationship to study drug)."}

Methods

• Use of study-specific recruitment materials (adult and caregiver brochures) provided as K2 recruitment materials (country-specific brochures present for DE, FR, NL, IT, ES, IE, FR-public).
• Provision of K1 recruitment arrangements documents describing recruitment and informed consent procedures (country-specific K1 documents present for multiple member states).
• Country-specific patient-facing materials including GP letters, patient cards and visit guides (documents available for Ireland and other member states).

Belgium

Earliest CTIS Part Ii Submission Date

25-04-2025

Latest Decision Or Authorization Date

22-09-2025

Processing Time Days

150

Number Of Sites

1

Number Of Participants

5

Germany

Earliest CTIS Part Ii Submission Date

01-12-2025

Latest Decision Or Authorization Date

12-01-2026

Processing Time Days

42

Number Of Sites

2

Number Of Participants

15

Ireland

Earliest CTIS Part Ii Submission Date

15-12-2025

Latest Decision Or Authorization Date

23-01-2026

Processing Time Days

39

Number Of Sites

1

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

24-04-2026

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

17

Number Of Sites

5

Number Of Participants

54

Spain

Earliest CTIS Part Ii Submission Date

10-03-2025

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

371

Number Of Sites

3

Number Of Participants

12

Italy

Earliest CTIS Part Ii Submission Date

14-04-2025

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

360

Number Of Sites

4

Number Of Participants

5

Norway

Earliest CTIS Part Ii Submission Date

07-12-2025

Latest Decision Or Authorization Date

20-03-2026

Processing Time Days

103

Number Of Sites

1

Number Of Participants

6

Primary sponsor

Full Name

Relay Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Worldwide Clinical Trials d.o.o.

Responsibilities

Sponsor duties include codes 1,12,15 (value: CRO), 2,5 as listed in CTIS third-party duties.

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Participant travel, payment and reimbursement services","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc. (79 5th Avenue address)","duties_or_roles":"Electronic capture of clinical outcome assessments (sponsorDuties code: 15)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Croatia","full_name":"Worldwide Clinical Trials d.o.o.","duties_or_roles":"sponsorDuties codes: 1, 12, 15 (value: CRO), 2, 5","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"EU central lab for sample receipt, triage to testing labs, storage (sponsorDuties code: 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"sponsorDuties code: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"sponsorDuties code: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Clinical Research LLC","duties_or_roles":"Central ECG (sponsorDuties code: 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Alliance Pharma Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eclinical Solutions LLC","duties_or_roles":"sponsorDuties code: 6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"MRI review and analysis; anonymization and storage of photographs (sponsorDuties code: 15)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Laboratory/Research/Testing facility"}