RLY-2608 for Overgrowth Syndrome

Recruiting at 12 trial locations

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

277 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of RLY-2608, an experimental treatment for individuals with PIK3CA Related Overgrowth Spectrum (PROS) and related malformations. The study consists of different parts to determine the optimal dose and compare RLY-2608 to a placebo, which contains no active drug. It seeks participants diagnosed with PROS or specific growth or malformation issues linked to the PIK3CA gene mutation. This trial may suit those dealing with these conditions. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that RLY-2608 is likely to be safe for humans?

Research has shown that RLY-2608 is being tested for safety in individuals with PIK3CA-related overgrowth conditions. This treatment targets a specific protein associated with these conditions. Although detailed safety information remains limited, the treatment has progressed to Phase 2 trials, indicating that earlier studies found it safe enough for broader testing.

Similar treatments in the past have demonstrated that side effects can occur, but they are usually mild, such as nausea or tiredness. However, researchers are still learning about reactions to RLY-2608. Prospective participants should consider this when deciding to join the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for overgrowth syndrome?

Researchers are excited about RLY-2608 because it offers a unique approach to treating overgrowth syndrome with a PIK3CA mutation. Unlike traditional treatments that might focus on managing symptoms or using broad-spectrum therapies, RLY-2608 specifically targets the PIK3CA mutation, which is directly involved in the condition. This precision targeting could lead to better outcomes with potentially fewer side effects. Additionally, RLY-2608 is being explored in flexible dosing regimens across different age groups, which could make it a versatile option for both pediatric and adult patients.

What evidence suggests that RLY-2608 might be an effective treatment for Overgrowth Syndrome?

Research has shown that RLY-2608, a drug targeting specific genetic changes, may help treat conditions like PIK3CA-Related Overgrowth Spectrum (PROS). This trial will evaluate RLY-2608 across various treatment arms, including different age groups and dose escalation designs. The treatment blocks the mutated gene responsible for abnormal cell growth. Early findings suggest that RLY-2608 can shrink overgrowths and improve symptoms in people with these conditions. Initial studies indicated that patients experienced fewer side effects compared to other treatments. These promising results suggest that RLY-2608 could become a new option for managing PROS. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06789913

NCT06789913 | A Phase 2 Study of Mutant-selective PI3Kα ... 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 PIK ...

2. uclahealth.org uclahealth.org/clinical-trials/phase-2-study-mutant-selective-pi3ka-inhibitor-rly-2608

A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY ... 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 ...

3. texaschildrens.org texaschildrens.org/departments/cancer-and-hematology-center/clinical-trials-and-novel-therapies/phase-2-study-mutant

Vascular Anomalies Center A Phase 2 Study of Mutant- ... This Phase 2 study evaluates the safety and effectiveness of the RLY-2608 medication in children and adults with PIK3CA-related overgrowth conditions.

4. clinicaltrials.eu clinicaltrials.eu/trial/study-of-rly-2608-for-adults-and-children-with-pik3ca-related-overgrowth-and-malformations/

Study of RLY-2608 for Adults and Children with PIK3CA- ... This clinical trial explores the effects of RLY-2608, a potential treatment for the PIK3CA-Related Overgrowth Spectrum and associated ...

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/pik3ca-related-overgrowth-spectrum

PIK3CA-Related Overgrowth Spectrum clinical trials at UCSF This is a 3-part Phase 2 randomized study evaluating the safety and efficacy of the mutant-selective PI3Kα inhibitor, RLY-2608, in adults ...

6. trialx.com trialx.com/clinical-trials/listings/297184/a-phase-2-study-of-mutant-selective-pi3k-inhibitor-rly-2608-in-adults-and-children-with-pik3ca-related-overgrowth-spectrum-and-malformations-driven-by-pik3ca-mutation/

A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY ... 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 ...

7. ctv.veeva.com ctv.veeva.com/study/a-phase-2-study-of-mutant-selective-pi3ka-inhibitor-rly-2608-in-adults-and-children-with-pik3ca-re

A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY ... 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 PIK ...

8. relaytx.com relaytx.com/patients/

Patients In a global Phase 2 study, we are currently evaluating the safety and efficacy of the mutant-selective PI3Kα inhibitor, RLY-2608, in adults and children with ...

9. medchemexpress.com medchemexpress.com/rly-2608.html?srsltid=AfmBOooARgVocuSViQaE9xFB5fzwmWs-GtjS9u_NONWiFWYgGaprvXjX

Zovegalisib (RLY-2608) | PI3Ka Inhibitor Zovegalisib (RLY-2608) is an orally active first-in-class allosteric mutant-selective inhibitor of PI3Ka with anti-tumor activity.