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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Relay Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

21 Nov 2025 → ongoing

Decision date (initial)

2025-05-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Relay Therapeutics Inc.

External identifiers

EU CT number

2024-518895-30-00

ClinicalTrials.gov

NCT06789913

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

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 as assessed by volumetric response rate

Secondary objectives 7

1. Parts 1 and 2: - To assess the PK of RLY-2608
2. Parts 1 and 2: - To characterize preliminary efficacy of RLY-2608
3. Parts 1 and 2: - To assess PIK3CA mutational status in lesional fluid and/or tissue
4. Part 3: - To assess changes in clinical reported outcome assessments in participants treated with RLY-2608 compared to placebo
5. Part 3: - To assess changes in the sum of target lesion volume over time in participants treated with RLY-2608 compared to placebo
6. Part 3: - To assess duration of response in participants treated with RLY-2608 compared to placebo
7. Part 3: - To determine the safety and tolerability of RP2D RLY-2608

Conditions and MedDRA coding

PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Lansky (<16 yo) or Karnofsky (≥16 yo) performance status of ≥50.
2. The participant must have a clinical diagnosis of PROS or a malformation within the ISSVA classifications
3. 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
4. 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 4

1. 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).
2. History of hypersensitivity to PI3K inhibitors.
3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
4. Clinically significant, uncontrolled cardiovascular disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Parts 1 and 2: RP2D(s) for Groups 1, 2, and 3
2. 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
3. Part 3: Percentage of participants with volumetric response at Week 24

Secondary endpoints 10

1. Parts 1 and 2: Percentage of participants with volumetric response at Weeks 12 and 24
2. Parts 1 and 2: Percent change from baseline in lesion volume by blinded independent central review (BICR)
3. 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
4. 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
5. Part 3: Percentage of participants with improvement compared to baseline based on PGI-S, PGI-C and IGIC of RLY-2608 compared to placebo
6. Part 3: Change from baseline by age-appropriate PROMIS Profile
7. Part 3: Change from baseline in EQ-5D, EQ-5D-Y, or EQ-5D-Y Proxy
8. Part 3: Percent change from baseline in lesion volume by BICR
9. 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
10. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Relay Therapeutics Inc.

Sponsor organisation

Relay Therapeutics Inc.

Address

60 Hampshire Street

City

Cambridge

Postcode

02139-1548

Country

United States

Scientific contact point

Organisation

Relay Therapeutics Inc.

Contact name

Clinical Operations

Public contact point

Organisation

Relay Therapeutics Inc.

Contact name

Clinical Operations

Third parties 12

Locations

7 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 158 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications