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

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 Update: Apr 14, 2021

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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. 

Study Description

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

Breast Cancer
Phase 2
Overall status 
Enrollment count 
390 participants
Start date 
Aug 14, 2017
Completion date 
Jul 15, 2022
18 Years and older (Adult, Older Adult)


300 mg; oral; once daily
500 mg; intramuscular injection on Days 1, 15 on Cycle 1 and Day 1 at each cycle thereafter
2.5 mg; oral; once daily
Every 28 days (only for men in cohort B and premenopausal women). Administered as injectable subcutaneous implant (3.6 mg)
Every 28 days (only for men in cohort B and premenopausal women). Administered as injectable intramuscular depot (7.5 mg)

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

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

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.

Study Locations

United States
Beverly Hills Cancer Center
Beverly Hills, 90211
United States
Mercy Medical Center
Baltimore, 21202
United States
Northwest Medical Specialists
Tacoma, 98405
United States
Novartis Investigative Site
Barcelona, 08035


Novartis Pharmaceuticals
Novartis Pharmaceuticals

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