NCT06789913 · Relay Therapeutics, Inc.
A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation
What this study is about
This is a 3-part Phase 2 randomly assigned study evaluating the safety and effectiveness of the mutant-selective PI3Kα inhibitor, RLY-2608, in adults and children with PIK3CA Related Overgrowth Spectrum (PROS) and malformations driven by PIK3CA mutation.
View original scientific description
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.
Interventions
DRUG
RLY-2608
RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.
DRUG
Placebo
RLY-2608 matched-placebo
Primary outcome measures
Parts 1 and 2: Determination of a recommended phase 2 dose RP2D(s) for Groups 1, 2, and 3
Time frame: Cycle 1 of treatment and at the end of every cycle until study discontinuation
Parts 1 and 2: Occurrence/frequency of Adverse Events (AEs), changes in vital signs, ECGs, and safety laboratory tests and their relationship to the study drugs (safety and tolerability).
Time frame: Cycle 1 of treatment and at the end of every cycle until study discontinuation
Part 3: Percentage of participants with volumetric Response.
Time frame: Baseline, Week 24
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- The participant must have a clinical diagnosis of PROS or a malformation within the ISSVA 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. Some participants may be eligible without a documented PIK3CA mutation as long as no other genetic driver has been documented.
- Lansky (\<16 yo) or Karnofsky (≥16 yo) performance status of ≥50.
- 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. Key
Exclusion criteria
- 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
- Received disease-directed therapy prior to the first dose of study drug: 1. Systemic therapy o
Where
- Phoenix, Arizona
- Little Rock, Arkansas
- Los Angeles, California
- Palo Alto, California
- San Francisco, California
- Aurora, Colorado
- Atlanta, Georgia
- Indianapolis, Indiana
- Baltimore, Maryland
- Boston, Massachusetts
- Grand Rapids, Michigan
- Rochester, Minnesota
And 8 more locations — see the full list below.
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 12, 2026 · Source of record for eligibility and locations