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Zovegalisib

Phase 3

PIK3CA Mutation | Small molecule | Oncology |Relay Therapeutics, Inc.|Last Updated: Sep 3, 2026

Development status

Highest phase Phase 3
Registered trials 1 across 1 sponsor since May 2025

Target and mechanism

Molecular targetPIK3CA
Target class-Lisib (Pi3k)
ModalitySmall molecule

Also known as RLY-2608

Success Probability

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Market & Valuation

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Trial Design

RandomizedCONTROLLEDDMC
Total Trials2
Total Enrollment1,470

FDA Designations

BREAKTHROUGH_THERAPY

Clinical trial landscape

Zovegalisib · 3 trials · 16 indications

Phase 3 1Phase 2 1Phase 1 1
NCT06982521Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast CancerPIK3CA Mutation
RECRUITING540 Analytics
PHASE3RECRUITING
Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer
PIK3CA MutationUnlock trial analytics

Study Endpoints

Primary Endpoints

Progression-Free Survival (PFS) within the overall and kinase population by blinded independent central review (BICR)
The time from date of randomization until radiographic progression per RECIST v1.1, or death due to any cause, up to approximately 77 months
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

Overall Survival (OS) within the overall and kinase populations
The time from randomization to the date of death by any cause, up to approximately 77 months
PFS by Investigator within the overall and kinase populations
The time from date of randomization until radiographic progression per RECIST v1.1, or death due to any cause, up to approximately 77 months
Objective Response Rate (ORR) within the overall and kinase populations
Up to approximately 77 months
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Zovegalisib + fulvestrantEXPERIMENTALZovegalisib + fulvestrant combination for participants with HR+/HER2- advanced breast cancer
capivasertib + fulvestrantACTIVE_COMPARATORcapivasertib + fulvestrant combination for participants with HR+/HER2- advanced breast cancer
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
ZovegalisibDRUG400 mg orally BID administered daily on a 28-day treatment cycle
CapivasertibDRUG400mg orally BID administered on an intermittent weekly dosing schedule. Patients will dose on Days 1 through 4 each week of a 28-day treatment cycle
FulvestrantDRUG500 mg intramuscularly administered on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (28-day treatment cycle)
RLY-2608DRUGRLY-2608 is a mutant-selective, oral PI3Kα inhibitor.
PlaceboDRUGRLY-2608 matched-placebo
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 Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites231

Inclusion Criteria: * Patient has ECOG performance status of 0-1 * One or more known primary oncogenic PIK3CA mutation(s) * Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with a gonadotropin-releasing ...

Countries:United StatesArgentinaAustraliaAustriaBelgiumBrazilBulgariaCanadaCzechiaDenmarkFranceGermanyGreeceHong KongItalyNetherlandsPolandPortugalSingaporeSouth KoreaSpainSwitzerlandTaiwanUnited KingdomIreland
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Recent Changes (Last 90 Days)

LOWSep 3, 2026NCT06982521lastUpdatePostDate: changed
LOWSep 3, 2026NCT06982521lastUpdatePostDate: changed
LOWAug 25, 2026NCT06789913lastUpdatePostDate: changed
LOWAug 25, 2026NCT06789913lastUpdatePostDate: changed
LOWAug 12, 2026NCT06789913lastUpdatePostDate: changed
LOWAug 12, 2026NCT06789913lastUpdatePostDate: changed
MEDIUMAug 5, 2026NCT06982521lastUpdatePostDate: changed
LOWJul 8, 2026NCT06982521lastUpdatePostDate: changed
LOWJul 8, 2026NCT06982521lastUpdatePostDate: changed

Frequently asked questions about Zovegalisib

What is Zovegalisib used for?

Zovegalisib is an investigational small molecule being developed for PIK3CA-mutant cancers and PIK3CA-Related Overgrowth Spectrum (PROS). Its lead programs include locally advanced or metastatic PIK3CA-mutant HR+/HER2- breast cancer and PROS with malformations driven by PIK3CA mutation, including lymphatic and vascular malformations.

What does Zovegalisib target?

Zovegalisib targets PIK3CA, the gene encoding the PI3K alpha isoform. It is described as a mutant-selective PI3K alpha inhibitor, part of the -lisib PI3K inhibitor class, meaning it is designed to act on the mutant form of the target. It is a small molecule given orally.

Who is developing Zovegalisib?

Zovegalisib is being developed by Relay Therapeutics, Inc., which trades under the ticker RLAY. The company is running the clinical program for the drug across breast cancer and PIK3CA-Related Overgrowth Spectrum indications.

What phase is Zovegalisib in?

Zovegalisib is in Phase 3 development. It is investigational and has not been approved by the FDA. The FDA has granted it Breakthrough Therapy designation. The Phase 3 program is evaluating the drug in PIK3CA-mutant HR+/HER2- breast cancer, while earlier-stage studies cover additional indications.

What clinical trials is Zovegalisib in?

Zovegalisib is being studied in three recruiting trials. NCT06982521 is a Phase 3 study in PIK3CA-mutant HR+/HER2- breast cancer. NCT06789913 is the Phase 2 ReInspire study in PIK3CA-Related Overgrowth Spectrum. NCT05216432 is the first-in-human Phase 1 study in advanced solid tumors and breast cancer.

Is Zovegalisib the same as RLY-2608?

Yes, Zovegalisib is the same drug as RLY-2608. RLY-2608 is the earlier code name used for the compound in trial titles and publications, while Zovegalisib is the current name. Both refer to the mutant-selective PI3K alpha inhibitor developed by Relay Therapeutics.