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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

Banner MD Anderson Cancer Center
Gilbert, Arizona 85234

Beverly Hills Cancer Center
Beverly Hills, California 90211

City of Hope National Medical Center
Duarte, California 91010

Cedars-Sinai Medical Center
Los Angeles, California 90048

Stanford Women's Cancer Center
Palo Alto, California 94304

University of California, Davis Comprehensive Cancer Center
Sacramento, California 95817

University of California San Diego Moores Cancer Center
San Diego, California 92037

University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center
San Francisco, California 94158

Kaiser Permanente Medical Center
Vallejo, California 94589

Rocky Mountain Cancer Centers, LLP
Longmont, Colorado 80504

Yale-New Haven Hospital-Yale Cancer Center
New Haven, Connecticut 06510

Medical Oncology Hematology Consultants, P.A.
Newark, Delaware 19713

Georgetown University Medical Center
Washington D.C., District of Columbia 20007

AdventHealth
Altamonte Springs, Florida 32701

Florida Cancer Specialists-South
Fort Myers, Florida 33901

Cancer Care Centers of Brevard, Inc
Palm Bay, Florida 32909

Rush University Medical Center
Chicago, Illinois 60607

Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois 60611

Community Health Network, Inc
Indianapolis, Indiana 46250

University of Kansas Cancer Center
Westwood, Kansas 66205

Cancer Center of Kansas
Wichita, Kansas 67214

Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins
Baltimore, Maryland 21287

Tufts Medical Center
Boston, Massachusetts 02111

Dana Farber Cancer Institute
Boston, Massachusetts 02215

University of Michigan
Ann Arbor, Michigan 48109

Profound Research LLC
Royal Oak, Michigan 48073

Minnesota Oncology Hematology, P.A.
Minneapolis, Minnesota 55404

University of Mississippi Medical Center
Jackson, Mississippi 39213

Washington University School of Medicine- Siteman Cancer Center
St Louis, Missouri 63108

Nebraska Cancer Specialists
Omaha, Nebraska 68130

Renown Health Medical Oncology
Reno, Nevada 89502

John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey 07601

Rutgers Cancer Institute
New Brunswick, New Jersey 08901

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York 10016

Icahn School of Medicine at Mount Sinai
New York, New York 10029

Columbia University Irving Medical Center
New York, New York 10032

Memorial Sloan-Kettering Cancer Center
New York, New York 10065

Oregon Health & Science University, Knight Cancer Institute
Portland, Oregon 97210

Avera Cancer Institute
Sioux Falls, South Dakota 57105

Tennessee Cancer Specialists
Knoxville, Tennessee 37909

Tennessee Oncology, PLLC
Nashville, Tennessee 37203

Texas Oncology Central/South
Austin, Texas 78731

Texas Oncology DFW
Dallas, Texas 75246

University of Texas Southwestern Medical Center
Dallas, Texas 75390

Houston Methodist Hospital Cancer Center
Houston, Texas 77030

The University of Texas M.D. Anderson Cancer Center
Houston, Texas 77030

Baylor Scott and White Medical Center
Temple, Texas 76508

Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah 84112

Virginia Cancer Specialists, PC
Fairfax, Virginia 22031

Virginia Oncology Associates
Norfolk, Virginia 23502

University of Wisconsin Carbone Cancer Center- University Hospital
Madison, Wisconsin 53792

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.