NCT06982521Recruiting
Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer
Summary
This is a global, multicenter, open-label, randomized Phase 3 study comparing the efficacy and safety of RLY-2608 (zovegalisib) + fulvestrant to capivasertib + fulvestrant for the treatment of patients with HR+/HER2- ABC with PIK3CA mutation following recurrence or progression on or after treatment with a CDK4/6 inhibitor.
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 hormone (GnRH) agonist. Patients are to have commenced treatment with a GnRH agonist at least 2 weeks prior to randomization and must be willing to continue on it for the duration of the study. • Histologically or cytologically confirmed diagnosis of HR+/HER2- locally advanced or metastatic breast cancer (ABC) with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent • Measurable disease per RECIST v1.1 or evaluable bone-only disease. • Must have radiological evidence of progression on or after previous treatment for HR+/HER2- ABC with: 1. At least 1 and no more than 2 lines of endocrine therapy (ET) in the (neo)adjuvant setting with recurrence on or within 12 months of completion or in the ABC setting 2. Only 1 prior line of CDK4/6 inhibitor therapy in one of the following settings: 1. CDK4/6 inhibitor + ET in the ABC setting 2. CDK4/6 inhibitor therapy in the adjuvant setting if progression occurred during or within 12 months of completion of adjuvant CDK4/6 inhibitor with ET 3. Patients who progressed during or within 12 months of completion of adjuvant CDK4/6 inhibitor and after receiving CDK4/6 inhibitor therapy in the advanced setting are considered to have had \>1 prior line of CDK4/6 inhibitor and are not eligible
Exclusion criteria
• Prior treatment with any of the following: 1. CDK2 inhibitors. Prior treatment with other investigational CDK inhibitors could be permitted upon discussion and approval from the Sponsor 2. PIK3, AKT, or mTOR inhibitors or any agent whose mechanism of action is the inhibit the PIK3/AKT/mTOR pathway 3. Immunotherapy 4. Antibody drug conjugates • Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥ 140 mg/dL (7.8 mmol/L), or glycosylated hemoglobin (HbA1c) ≥7.0% (≥ 53 mmol/mol). • Clinically significant, uncontrolled cardiovascular disease • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events • Known active uncontrolled or symptomatic CNS metastases associated with progressive neurological symptoms or requiring ongoing corticosteroids or anticonvulsants for symptomatic control • Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease • History of hypersensitivity to fulvestrant or drugs in a similar class as fulvestrant, zovegalisib, or capivasertib, including their excipients • Known activating AKT mutations, loss-of-function PTEN mutations, or loss of PTEN expression resulting in oncogenic pathway activation downstream of PI3K
Contacts
The trial team's contact details are shown on request.
See the official trial record- Status
- Recruiting
- Phase
- Phase 3
- Study type
- Interventional
- Countries
- Switzerland, France, Germany, Italy, Austria, United States, Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Czechia, Denmark, Greece, Hong Kong, Ireland, Netherlands, Poland, Portugal, Romania, Singapore, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom
- Sponsor
- Relay Therapeutics, Inc.(Industry)
- Protocol no.
- RLY-2608-102
- Conditions
- PIK3CA Mutation, HER2- Negative Breast Cancer, Hormone Receptor Positive Tumor, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer
- Interventions
- Drug
Treatments studied
- Zovegalisib
- Capivasertib
- Fulvestrant
Locations · 243
- Aarau, SwitzerlandTumor Zentrum AarauRecruiting at this site
- Basel, SwitzerlandUniversity Hospital of BaselRecruiting at this site
- Angers, FranceL'Institut de Cancérologie de l'Ouest (ICO) - AngersRecruiting at this site
- Besançon, FranceCHU BesanconRecruiting at this site
- Bobigny, FranceHopital AvicenneRecruiting at this site
- Bordeaux, FranceInstitut BergonieRecruiting at this site
- Caen, FranceCentre François BaclesseRecruiting at this site
- Lyon, FranceCentre Leon BerardRecruiting at this site
- Lyon, FranceHôpital Privé Jean MermozRecruiting at this site
- Marseille, FranceHôpital de la TimoneRecruiting at this site
- Montpellier, FranceCentre de Cancérologie du Grand MontpellierRecruiting at this site
- Nice, FranceCentre Antoine LacassagneRecruiting at this site
- Paris, FranceInstitut CurieRecruiting at this site
- Paris, FranceHôpital Saint Louis - SENOPOLERecruiting at this site
- Plérin, FranceHôpital Privé des Côtes d'ArmorRecruiting at this site
- Saint-Herblain, FranceInstitut de Cancerologie de l'Ouest ICORecruiting at this site
- Thonon-les-Bains, FranceHopital du LemanRecruiting at this site
- Toulouse, FranceInstitut Claudius RegaudRecruiting at this site
- Vandœuvre-lès-Nancy, FranceInstitut de Cancérologie de LorraineRecruiting at this site
- Vantoux, FranceUNEOS - Hopital Robert SchumanRecruiting at this site
- Villejuif, FranceInstitut Gustave RoussyRecruiting at this site
- Aschaffenburg, GermanyMVZ Klinikum AschaffenburgRecruiting at this site
- Bottrop, GermanyMarienhospital Bottrop gGmbHRecruiting at this site
- Dresden, GermanyUniversitätsklinikum Carl Gustav Carus TU DresdenRecruiting at this site
- Eggenfelden, GermanyStudienzentrale für das MVZ Eggenfelden GbRRecruiting at this site
- Erlangen, GermanyUniversitätsklinikum ErlangeRecruiting at this site
- Freiburg im Breisgau, GermanyUniversitaetsklinikum FreiburgRecruiting at this site
- Freiburg im Breisgau, GermanyPraxis fuer Interdisziplinaere Onkologie und HaematologieRecruiting at this site
- Krefeld, GermanyHelios Klinikum KrefeldRecruiting at this site
- Mannheim, GermanyUniversitaetsmedizin MannheimRecruiting at this site
In total, worldwide, all 243 sites listed in the registry are recruiting.
Site status per the ClinicalTrials.gov registry (last update posted: October 5, 2026).
This status may have changed and says nothing about your eligibility: before taking any step, check with your oncologist or the site.
+ 213 more locations
See also
Other versions
These results are indicative and do not replace medical advice — discuss them with your doctor.