RLY-2608 for Overgrowth Syndrome

Overseen By Relay Therapeutics, Inc

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Relay Therapeutics, Inc.

Must not be taking: PI3K inhibitors

Disqualifiers: Cardiovascular disease, QTc prolongation, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

280 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a 3-part Phase 2 randomized study evaluating the safety and efficacy of the mutant-selective PI3Kα inhibitor, 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.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic therapy (medications that affect the entire body) at least 14 days before starting the study drug, or longer if the medication stays in your body for a while. If you've had antibody therapy, you need to stop it 28 days before the trial.

Eligibility Criteria

This trial is for adults and children with PIK3CA Related Overgrowth Spectrum (PROS) or malformations classified by ISSVA. Participants must have a certain level of physical ability, agree to provide tissue samples, and have specific PIK3CA mutations targeted by the drug RLY-2608.

Inclusion Criteria

I have been diagnosed with PROS or a related malformation.

I am mostly able to do daily activities despite my illness.

My cancer has a specific mutation targeted by certain cancer drugs.

Exclusion Criteria

I have a serious heart condition that is not under control.

History of hypersensitivity to PI3K inhibitors

I haven't had recent cancer treatment or surgery before starting the study drug.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Selection

Part 1 involves dose selection with a dose escalation design for RLY-2608 in pediatric participants

8 weeks

Multiple visits for dose escalation

Basket Design

Part 2 is a basket design with exploratory single-arm cohorts for various subpopulations

12 weeks

Regular visits for monitoring and assessment

Randomized Study

Part 3 is a randomized, double-blinded study comparing RLY-2608 to placebo

16 weeks

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• RLY-2608

Trial Overview The study tests RLY-2608, a drug aimed at selectively inhibiting mutant PI3Kα in patients with PROS and related malformations. It's divided into three parts: dose selection, exploratory cohorts for subpopulations, and a placebo-controlled comparison.

Participant Groups

Group I: Part 3, Arm 1 Experimental Treatment 1 Intervention

Adult (\>18 yo), and adolescent and pediatric (6 to \<18 yo) participants with PROS and malformations with PIK3CA mutation will be randomized to receive RLY-2608 at oral dose determined during Part 1/2 versus placebo.

Group II: Part 2, Group 3 Experimental Treatment 1 Intervention

Dose expansion cohorts for participants 2 to \<6 years old with PROS or malformations with PIK3CA mutation. Oral dose of RLY-2608 as determined during Part 1.

Group III: Part 2, Group 2 Experimental Treatment 1 Intervention

Dose expansion cohorts for participants 6 to \<12 years old with PROS or malformations with PIK3CA mutation. Oral dose of RLY-2608 as determined during Part 1.

Group IV: Part 2, Group 1 Experimental Treatment 1 Intervention

Dose expansion single-arm cohorts for various subpopulations of participants ≥12 years old with PROS or malformations with PIK3CA mutation. Oral dose of RLY-2608 as determined during Part 1.

Group V: Part 1, Group 3 Experimental Treatment 1 Intervention

Part 1, Group 3: RLY-2608 for participants 2 to \<6 years old with PROS or malformations with PIK3CA mutation. RLY-2608 will be studied in pediatric participants in a dose escalation design.

Group VI: Part 1, Group 2 Experimental Treatment 1 Intervention

RLY-2608 for participants 6 to \<12 years old with PROS or malformations with PIK3CA mutation. RLY-2608 will be studied in pediatric participants in a dose escalation design.

Group VII: Part 1, Group 1 Experimental Treatment 1 Intervention

RLY-2608 for patients ≥12 years old with PROS or malformations with PIK3CA mutation. Multiple doses of RLY-2608 for oral administration.

Group VIII: Part 3, Arm 2 Placebo Group 1 Intervention

Adult (\>18 yo), and adolescent and pediatric (6 to \<18 yo) participants with PROS and malformations with PIK3CA mutation will be randomized to receive placebo.

Who Is Running the Clinical Trial?

Relay Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

1,900+