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RLY-2608

Phase 2

PIK3CA-Related Overgrowth Spectrum (PROS) | Small molecule | Oncology |Relay Therapeutics, Inc.|Last Updated: Aug 25, 2026

Success Probability

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Market & Valuation

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Trial Design

RandomizedPLACEBO_CONTROLLED
Total Trials1
Total Enrollment277

FDA Designations

No designations recorded

Clinical trial landscape

RLY-2608 · 2 trials · 14 indications

Phase 2 1Phase 1 1
NCT06789913A 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 (The ReInspire Study)PIK3CA-Related Overgrowth Spectrum (PROS)
RECRUITING277 Analytics
PHASE2RECRUITING
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 (The ReInspire Study)
PIK3CA-Related Overgrowth Spectrum (PROS)Unlock trial analytics

Study Endpoints

Primary Endpoints

Parts 1 and 2: Determination of a recommended phase 2 dose RP2D(s) for Groups 1, 2, and 3
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).
Cycle 1 of treatment and at the end of every cycle until study discontinuation
Part 3: Percentage of participants with volumetric Response.
Baseline, Week 24
Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of RLY-2608 as a single agent
Cycle 1 (4-week cycle) of treatment for MTD and at the end of every cycle (4-week cycles) for RP2D until study discontinuation, approximately 24 months
Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of RLY-2608 in combination with fulvestrant
Cycle 1 (4-week cycle) of treatment for MTD and at the end of every cycle (4-week cycles) for RP2D until study discontinuation, approximately 24 months
Determination of maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of RLY-2608 in combination with fulvestrant and a CDK 4/6 inhibitor (palbociclib, ribociclib), and in combination with CDK4 inhibitor (PF-07220060) and fulvestrant
Cycle 1 (4-week cycle) of treatment for MTD and at the end of every cycle (4-week cycles) for RP2D until study discontinuation, approximately 24 months
Number of patients with adverse events and serious adverse events of RLY-2608 as a single agent
Every cycle (4-week cycles) until study discontinuation, approximately 24 months
Number of patients with adverse events and serious adverse events of RLY-2608 in combination with fulvestrant
Every cycle (4-week cycles) until study discontinuation, approximately 24 months
Number of patients with adverse events and serious adverse events of RLY-2608 in combination with fulvestrant and a CDK 4/6 inhibitor (palbociclib, ribociclib), and in combination with CDK4 inhibitor (PF-07220060) and fulvestrant
Every cycle (4-week cycles) until study discontinuation, approximately 24 months

Secondary Endpoints

Part 1 and 2: Percent change from baseline in lesion volume
Baseline, Week 24
Part 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
Approximately every 3 months for approximately the first year, and then every 6 months during treatment
Part 1 and 2: Percentage of participants with volumetric response
Baseline, week 12, week 24
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Part 1, Group 1EXPERIMENTALRLY-2608 for patients ≥12 years old with PROS or malformations with PIK3CA mutation. Multiple doses of RLY-2608 for oral administration.
Part 1, Group 2EXPERIMENTALRLY-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.
Part 1, Group 3EXPERIMENTALPart 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.
Part 2, Group 1EXPERIMENTALDose 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.
Part 2, Group 2EXPERIMENTALDose 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.
Part 2, Group 3EXPERIMENTALDose 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.
Part 3, Arm 1EXPERIMENTALAdult (\>18 yo) 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.
Part 3, Arm 2PLACEBO_COMPARATORAdult (\>18 yo) and pediatric (6 to \<18 yo) participants with PROS and malformations with PIK3CA mutation will be randomized to receive placebo.
RLY-2608 for patients with unresectable or metastatic solid tumorsEXPERIMENTALMultiple doses of RLY-2608 for oral administration.
RLY-2608 + fulvestrant combination for HR+ HER2- locally advanced or metastatic breast cancerEXPERIMENTALOral dose of RLY-2608 in addition to fulvestrant as determined during Part 1 Dose Escalation.
RLY-2608+fulvestrant+palbo125mg for HR+HER2- locally advanced metastatic breast cancerEXPERIMENTALOral dose of RLY-2608 in addition to fulvestrant and palbociclib 125mg as determined during Part 1 Dose Escalation.
RLY-2608+fulvestrant+ribo400mg for HR+HER2- locally advanced metastatic breast cancerEXPERIMENTALOral dose of RLY-2608 in addition to fulvestrant and ribociclib 400mg as determined during Part 1 Dose Escalation.
RLY-2608+fulvestrant+ribo600mg for HR+HER2- locally advanced metastatic breast cancerEXPERIMENTALOral dose of RLY-2608 in addition to fulvestrant and ribociclib 600mg as determined during Part 1 Dose Escalation.
RLY-2608+fulvestrant+PF-07220060 100 mg for HR+ HER2- locally advanced or metastatic breast cancerEXPERIMENTALOral dose of RLY-2608 in addition to fulvestrant and PF-07220060 100 mg as determined during Part 1 Dose Escalation
RLY-2608+fulvestrant+PF-07220060 300 mg for HR+ HER2- locally advanced or metastatic breast cancerEXPERIMENTALOral dose of RLY-2608 in addition to fulvestrant and PF-07220060 300 mg as determined during Part 1 Dose Escalation

Interventions

NameTypeDescription
RLY-2608DRUGRLY-2608 is a mutant-selective, oral PI3Kα inhibitor.
PlaceboDRUGRLY-2608 matched-placebo
FulvestrantDRUG500 mg fulvestrant is administered intramuscularly on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (where a cycle is 28 days).
Palbociclib 125mgDRUG125mg palbociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
Ribociclib 400mgDRUG400mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
Ribociclib 600mgDRUG600mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
PF-07220060 100mgDRUGPF-07220060 100 mg is taken orally twice daily at the same time with RLY-2608 during each 28-day cycle.
PF-07220060 300 mgDRUGPF-07220060 300 mg is taken orally twice daily at the same time with RLY-2608 during each 28-day cycle.
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Eligibility Criteria

Age Range2 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites40

Key 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...

Countries:United StatesAustraliaBelgiumFranceGermanyIrelandItalySpainUnited Kingdom
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Recent Changes (Last 90 Days)

LOWAug 25, 2026NCT06789913lastUpdatePostDate: changed
LOWAug 25, 2026NCT06789913lastUpdatePostDate: changed
LOWAug 12, 2026NCT06789913lastUpdatePostDate: changed
LOWAug 12, 2026NCT06789913lastUpdatePostDate: changed
LOWJun 12, 2026NCT06789913lastUpdatePostDate: changed
LOWJun 12, 2026NCT06789913lastUpdatePostDate: changed

Frequently asked questions about RLY-2608

What is RLY-2608 used for?

RLY-2608 is an investigational small molecule being studied for the treatment of cancers and conditions driven by PIK3CA mutations. It is being evaluated in advanced solid tumors, including HER2-negative and metastatic breast cancer, and in PIK3CA-Related Overgrowth Spectrum (PROS), a group of disorders involving overgrowth and vascular malformations.

What does RLY-2608 target?

RLY-2608 targets mutant PI3Kα, a form of the PI3K alpha enzyme that is mutated in certain cancers and overgrowth conditions. It is described as a mutant-selective PI3Kα inhibitor, meaning it is designed to act on the mutated version of the enzyme while potentially sparing normal PI3Kα activity.

Who is developing RLY-2608?

RLY-2608 is being developed by Relay Therapeutics, Inc., a biopharmaceutical company traded on the stock exchange under the ticker symbol RLAY. The company is conducting clinical trials of RLY-2608 in both oncology and rare disease indications.

What phase is RLY-2608 in?

RLY-2608 is in Phase 1 and Phase 2 clinical development. A Phase 1 study is evaluating it as a single agent and in combination with other therapies in advanced solid tumors and breast cancer, while a Phase 2 study is assessing it in adults and children with PIK3CA-Related Overgrowth Spectrum. It is investigational and not yet approved.

What clinical trials is RLY-2608 in?

RLY-2608 is being studied in two recruiting trials. NCT05216432 is a Phase 1 first-in-human study in advanced solid tumors and breast cancer, with an enrollment of 930 participants. NCT06789913 is a Phase 2 study in PIK3CA-Related Overgrowth Spectrum, enrolling 277 participants across multiple countries.

Is RLY-2608 the same as a PI3K inhibitor?

RLY-2608 is a PI3Kα inhibitor, specifically a mutant-selective one. It is designed to inhibit the alpha isoform of PI3K when it carries a mutation, which is relevant in certain cancers and overgrowth syndromes. It is not the same as pan-PI3K inhibitors that target multiple isoforms.