Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer Who Have Progressed on or After Prior Treatments

• Register: ClinicalTrials.gov
• Last refreshed on: 11 March 2024
• Main ID: NCT03056755
• Date of registration: 15/02/2017
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer Who Have Progressed on or After Prior Treatments BYLieve
• Scientific title: 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
• Date of first enrolment: August 14, 2017
• Target sample size: 383
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03056755
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Argentina, Belgium, Canada, Chile, Denmark, France, Germany, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Singapore, Spain, Taiwan, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patient is male or female 18 years or older

- Males or females with advanced (locoregionally recurrent or metastatic) 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 confirmed HER2-negative advanced breast cancer (aBC)

- Patient has histological and/or cytological confirmed ER+ and/or PgR+ 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:

- CDK 4/6 inhibitor treatment as last treatment regimen in cohorts A and B

- 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 a known hypersensitivity to alpelisib, fulvestrant, letrozole, goserelin
or leuprolide or to any of the excipients of alpelisib, fulvestrant, letrozole,
goserelin or leuprolide.

- 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
chronic 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 Necrolysis (TEN) or Drug Reaction
with Eosinophilia 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.

Other inclusion/exclusion criteria may apply



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Breast Cancer

Intervention(s)

Drug: Goserelin

Drug: Alpelisib

Drug: Fulvestrant

Drug: Leuprolide

Drug: Letrozole

Primary Outcome(s)

Percentage of participants who are alive without disease progression at 6 months [Time Frame: At 6 months]

Secondary Outcome(s)

Clinical benefit rate (CBR) for each cohort [Time Frame: Up to approximately 25 months]

Duration of response (DOR) [Time Frame: From date of first documented response to first documented progression or death, up to approximately 25 months]

Percentage of participants with clinical benefit as assessed by the Investigator during the extension phase [Time Frame: From end of core phase up to 12 months]

Progression free survival (PFS) on next line treatment PFS2) for each cohort [Time Frame: From date of first dose to date of first documented progression on next-line therapy or death, up to approximately 25 months]

Progression free survival (PFS) for each cohort [Time Frame: From date of first dose to date of first documented progression or death, up to approximately 25 months]

Overall survival (OS) for each cohort [Time Frame: From date of first dose and up to approximately 25 months]

Overall response rate (ORR) for each cohort [Time Frame: Up to approximately 25 months]

Secondary ID(s)

CBYL719X2402

2016-004586-67

Source(s) of Monetary Support

Please refer to primary and secondary sponsors