BYLieve: A Phase II, Multicenter, Open-label, Three-cohort, Non- Comparative Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole in Patients With PIK3CA Mutant, Hormone Receptor (HR) Positive, HER2-negative Advanced Breast Cancer (aBC), Who Have Progressed on or After Prior Treatments Identifier: NCT03056755 | Novartis reference number: CBYL719X2402 | Last updated on: June 2, 2020


All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.


Trial purpose

Study assessing the efficacy and safety of alpelisib plus fulvestrant or letrozole, based on prior endocrine therapy, in patients with PIK3CA mutation with advanced breast cancer who have progressed on or after prior treatments


Trial summary



Breast Cancer



Phase 2

study type


Interventional  (Clinical Trial)






18 Years and older   (Adult, Older Adult)

Accepts healthy volunteers



Estimated completion date


August 14, 2017

Estimated completion date


May 2, 2022

estimated enrolment


340 participants

Recruitment status




Eligibility criteria

Inclusion Criteria:

  • Patient is male or female 18 years or older
  • Males or females with advanced (locoregionally recurrent or metatstatic) breast cancer not amenable to curative therapy
  • In case of women, both premenopausal and postmenopausal patients are allowed to be included in study; menopausal status is relevant for the requirement of LHRH agonist (examples for use in this study include but not limited to goserelin, leuprolide or locally available treatment) to be used concomitantly with alpelisib and letrozole/fulvestrant

    1. Patient is postmenopausal woman defined as either:

      • Prior bilateral oophorectomy or
      • Age ≥60 or
      • Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and/or estradiol in the postmenopausal range per local normal range.

      If patient is taking tamoxifen or toremifene and age <60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range.

      Note: For women using therapy-induced amenorrhea other than ovarian radiation, goserelin or leuprolide, etc., serial measurements of FSH and/or estradiol are needed to ensure menopausal status

    2. Patient is premenopausal defined as either:

      • Patient had last menstrual period within the last 12 months or
      • If on tamoxifen or toremifene with in the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, or
      • In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range
  • Patient has histological and/or cytological confirmed ER+ and/or PgR+ aBC
  • Patient has confirmed HER2-negative advanced breast cancer (aBC)
  • Patient has a PIK3CA mutation confirmed by Novartis designated central lab or patient has a pathology report confirming PIK3CA mutant status by certified laboratory (using validated PI3KCA mutation assay) either from tissue or blood and must (mandatory) send tumor tissue to Novartis designated central lab for confirmation of mutational status
  • Patient must have:

    • Documented evidence of tumor progression on or after CDK 4/ 6 inhibitor combination treatment; CDK 4/6 inhibitor must be the last treatment regimen prior to study entry,
    • AI treatment (either in adjuvant or metastatic setting) and received systemic chemotherapy or ET(as monotherapy or in combination except CDK 4/6i + AI) as last treatment regimen in cohort C
    • Maintenance therapies, where applicable, must be regarded as part of the main treatment.
    • No more than two (2) prior anti-cancer therapies for aBC
    • Received no more than one prior regimen of chemotherapy in the metastatic setting
  • Patient has either measurable disease per RECIST v1.1 or at least one predominantly lytic bone lesion must be present
  • ECOG performance status ≤ 2
  • Patient has fasting plasma glucose (FPG) ≤140 mg/dL (7.7 mmol/L) and glycosylated hemoglobin (HbA1c) ≤ 6.4% (both criteria have to be met)
  • Patient has adequate bone marrow, coagulation, liver and renal function

Exclusion Criteria:

  • Patient has known hypersensitivity to alpelisib, fulvestrant or letrozole
  • Patient has received prior treatment with any PI3K inhibitors
  • Patient with an established diagnosis of diabetes mellitus type I or uncontrolled type II
  • Patient has a concurrent malignancy or malignancy within 3 years of study screening period, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanoma skin cancer or curatively resected cervical cancer
  • Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to enrollment, and who has not recovered to grade 1 or better from related side effects of such therapy
  • History of acute pancreatitis within 1 year of screening or past medical history of pancreatitis
  • Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:

    • At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
    • Clinically stable CNS tumor at the time of screening untreated or without evidence of progressions for at least 4 weeks after treatment as determined by clinical examination and brain imaging (MRI or CT) during screening period and stable low dose of steroids for 2 weeks prior to initiating study treatment
  • Patient with severe liver impairment (Child Pugh score B/C)
  • Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs
  • Patient has documented pneumonitis/interstitial lung disease which is active and requiring treatment
  • Patient has a history of severe cutaneous reactions like Stevens-Johnson-Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necroloysis (TEN) or Drug Reaction with Eosinphilia and Systemic Symptoms (DRESS).
  • Patient is concurrently using other anti-cancer therapy. All anti-cancer therapy must be discontinued prior to day one of study treatment.
  • Subjects with unresolved osteonecrosis of the jaw.



Drug: alpelisib

Drug: fulvestrant

Drug: letrozole

Drug: Goserelin

Drug: Leuprolide


Trial locations

United States, Arizona
Banner MD Anderson Cancer Center    Recruiting
Gilbert, Arizona, United States, 85234
Contact: Tracey Tichenor    480-256-6444    [email protected]   
Principal Investigator: Shakeela Bahadur    
Mayo Clinic (Arizona)    Recruiting
Phoenix, Arizona, United States, 85054
Contact: Charanjit Singh    480-342-6429    [email protected]   
Principal Investigator: Donald W Northfelt         

United States, California
Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M.C    Recruiting
Anaheim, California, United States, 92807
Contact: Sindhuja Annepally    808-432-8587    [email protected]   
Principal Investigator: Jennifer Carney        

Beverly Hills Cancer Center    Recruiting
Beverly Hills, California, United States, 90211
Contact: Francisco Capilla    310-432-8900    [email protected]   
Principal Investigator: Linea Chap      
USC Norris Cancer Center    Recruiting
Los Angeles, California, United States, 90033
Contact: Margie Carranza    323-865-3955    [email protected]   
Principal Investigator: Janice Lu         

University of Calif Irvine Medical Center    Recruiting
Orange, California, United States, 92868
Contact: Pamela Diaz    714-456-5376    [email protected]   
Principal Investigator: Ritesh Parajuli         

Kaiser Permanente Southern California    Recruiting
San Diego, California, United States, 92120
Contact: Mathew Angela Douraghi    619-528-3955    [email protected]   
Principal Investigator: Jonathan Polikoff      

University of California, San Francisco    Recruiting
San Francisco, California, United States, 94115
Contact: Micah Viss    415-885-3789    [email protected]   
Principal Investigator: Hope S Rugo    
Cancer Research Collaboration, Inc    Recruiting
Santa Ana, California, United States, 92705
Contact: Andrea Provost    562-981-6101    [email protected]   
Principal Investigator: John Link         

United States, Connecticut
Yale University Yale Cancer Center    Recruiting
New Haven, Connecticut, United States, 06511
Contact: Trisha Burrello    203-737-2848    Tri[email protected]   
Principal Investigator: Andrea Silber         

United States, Florida
Miami Cancer Center at Mercy Hospital    Recruiting
Miami, Florida, United States, 33133
Principal Investigator: Ana Sandoval-Leon    
Advent Health Cancer Institute    Recruiting
Orlando, Florida, United States, 32804
Contact: Susan Dempsey-Walls    407-303-3235    [email protected]   
Principal Investigator: Carlos A. Alemany         

United States, Iowa
University of Iowa Hospitals and Clinics    Recruiting
Iowa City, Iowa, United States, 52242
Contact: Amanda Farmer    319-356-1826    [email protected]   
Principal Investigator: Sneha Phadke         

United States, Kansas
University of Kansas Cancer Center    Recruiting
Kansas City, Kansas, United States, 66205
Contact: Deborah Bayer    913-945-5052    [email protected]   
Principal Investigator: Qamar J Khan         

United States, Kentucky
University of Louisville Hospital/James Brown Cancer Ctr. SC    Recruiting
Louisville, Kentucky, United States, 40202
Contact: Teresa Roberts    502-562-4356    [email protected]   
Principal Investigator: Mounika Mandadi         

United States, Maryland
Mercy Medical Center    Recruiting
Baltimore, Maryland, United States, 21202
Contact: Lisa McConnell    410-332-1200    [email protected]   
Principal Investigator: David Andrew Riseberg        
Greater Baltimore Medical Center Cancer Center    Recruiting
Baltimore, Maryland, United States, 21204-6831
Contact: Kathryn Tower    410-528-3058    [email protected]   
Principal Investigator: Madhu Chaudhry    
Holy Cross Hospital Pharmacy    Recruiting
Silver Spring, Maryland, United States, 20910
Contact: Melin Vranesic       [email protected]   
Principal Investigator: Cheryl Aylesworth

United States, Massachusetts
Massachusetts General Hospital Neuroendocrine Unit    Recruiting
Boston, Massachusetts, United States, 02114
Contact: Shannon McLaughlin    617-724-0878    [email protected]   
Principal Investigator: Dejan Juric    
Lahey Clinic    Recruiting
Burlington, Massachusetts, United States, 01805
Contact: Amanda Pietras    781-744-2500    [email protected]   
Principal Investigator: Corrine Zarwan         

United States, Michigan
Josephine Ford Cancer Institute    Recruiting
Detroit, Michigan, United States, 48202
Contact: Marjorie Wood    313-916-2438    [email protected]   
Principal Investigator: Haythem Ali         

United States, Missouri
Washington University School of Medicine    Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Jill Anderson    314-362-9679    [email protected]   
Principal Investigator: Cynthia Ma         

United States, Montana
St Vincent Frontier Cancer Center    Recruiting
Billings, Montana, United States, 59102
Contact: Sabrina Leonhardt    406-238-6962    [email protected]   
Principal Investigator: Patrick Cobb         

United States, New Mexico
New Mexico Cancer Care Alliance    Recruiting
Albuquerque, New Mexico, United States, 87106
Contact: Harlie D Custer    505-925-0366    [email protected]   
Principal Investigator: Ursa Brown-Glaberman         

United States, New York
Memorial Sloane Kettering Cancer Center    Recruiting
New York, New York, United States, 10065
Contact: Katherine Whitaker    646-888-5341    [email protected]   
Principal Investigator: Pamela Drullinsky         

United States, Ohio
University Hospitals of Cleveland Seidman Cancer Center    Recruiting
Cleveland, Ohio, United States, 44106
Contact: Bethany Lawrence    216-844-5176    [email protected]   
Principal Investigator: Paula Silverman         

United States, Texas
Texas Oncology Charles A. Sammons Cancer Ctr    Recruiting
Dallas, Texas, United States, 75246
Contact: Danielle Koetter       [email protected]   
Principal Investigator: Joanne L Blum         

Texas Oncology P A SC-3    Recruiting
Dallas, Texas, United States, 75251
Contact    214-739-4175      
Principal Investigator: Kristi J. McIntyre    
Texas Oncology Houston Memorial City    Recruiting
Houston, Texas, United States, 77024
Contact: Nina Fru    +1 713467 1722    [email protected]   
Principal Investigator: Michelina Cairo    
Texas Oncology P A Plano East    Recruiting
Plano, Texas, United States, 75075
Contact    972-867-3577      
Principal Investigator: Christopher T Stokoe
Cancer Care Centers of South Texas HOAST CCC of So. TX- San Antonio(2)    Recruiting
San Antonio, Texas, United States, 78229
Contact: Barbara Dumond    210-656-7177    [email protected]   
Principal Investigator: Sharon T. Wilks         

UT Health San Antonio    Recruiting
San Antonio, Texas, United States, 78229
Contact: Marisa F Rodriguez    210-450-1366    [email protected]   
Principal Investigator: Virginia Kaklamani         

United States, Virginia
Virginia Oncology Associates SC    Recruiting
Norfolk, Virginia, United States, 23502
Contact    757-466-8683      
Principal Investigator: Michael A. Danso         

United States, Washington
Northwest Medical Specialists    Recruiting
Tacoma, Washington, United States, 98405
Contact: Patti Walsh    253-396-5329    [email protected]   
Principal Investigator: Sibel Blau         
Wenatchee Valley Medical Center    Recruiting
Wenatchee, Washington, United States, 98801
Contact: Sharon Barb    509-665-5800    [email protected]   
Principal Investigator: Lindsay Overton         

Have questions?

Call 1-888-669-6682 or email [email protected]