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Purpose

This is a global, multicenter, open-label, randomized Phase 3 study comparing the efficacy and safety of RLY-2608 + 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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 4 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. 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 or selective CDK4 inhibitors or any investigational therapies targeting cyclin dependent kinases 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, 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, RLY-2608, 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
RLY-2608 + fulvestrant 		RLY-2608 + fulvestrant combination for participants with HR+/HER2- advanced breast cancer
  • Drug: RLY-2608
    400 mg orally BID administered daily on a 28-day treatment cycle
  • Drug: Fulvestrant
    500 mg intramuscularly administered on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (28-day treatment cycle)
    Other names:
    • Faslodex
Active Comparator
capivasertib + fulvestrant 		capivasertib + fulvestrant combination for participants with HR+/HER2- advanced breast cancer
  • Drug: Capivasertib
    400mg 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
    Other names:
    • TRUQAP
  • Drug: Fulvestrant
    500 mg intramuscularly administered on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (28-day treatment cycle)
    Other names:
    • Faslodex

Recruiting Locations

University of Kansas Medical Center
Westwood 4281639, Kansas 4273857 66205

More Details

Status
Recruiting
Sponsor
Relay Therapeutics, Inc.

Study Contact

Relay Therapeutics, Inc
617-322-0731
ClinicalTrials@relaytx.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.