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

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 6

Inclusion Criteria

1. adult male or female * 18 years old at the time of consent
2. Patient has PIK3CA mutation confirmed by a Novartis designated laboratory,
or
Patient has a pathology report confirming PIK3CA mutant status It is also
mandatory to
provide a tumor sample collected after the most recent
progression or recurrence
3. Patient has a confirmed, HER2-negative aBC.
4. Patient is a men, or pre or postmenopausal woman.
Postmenopausal as defined:
* Prior bilateral oophorectomy
* Age *60
* Age <60 and amenorrhea for 12 or more months
Special requirements are required for premenopausal women.
5. Patient has a confirmed diagnosis of ER+ and/or PgR+ breast cancer , 6.
documented evidence of tumor progression
- cohort A and B : CDK 4/6 inhibitor treatment as last treatment regimen
- cohort C: AI treatment and received systemic chemotherapy or ET as last
treatment regimen , 7. Patients must have either:
Measurable disease, i.e., at least one measurable lesion as per RECIST v1.1
criteria
If no measurable disease is present, then at least one predominantly lytic bone
lesion must
be present
8. Patient has ECOG (Eastern Cooperative Oncology Group) Performance Status * 2
9. Males or females with advanced breast cancer not amenable to curative
therapy.

Exclusion Criteria

1. Patient has received prior treatment with any PI3K inhibitors
2. Patients with central nervous system (CNS) involvement unless they meet ALL
of the
following criteria:
* At least 4 weeks from prior therapy completion 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
3. Patient with clinically manifest diabetes mellitus, or documented steroid
induced diabetes
mellitus

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p> the proportion of patients who are alive without disease progression at 6<br /><br>months based on local investigator assessment using RECIST v1.1 in each cohort</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>PFS based on local investigator assessment using RECIST v1.1 in each cohort<br /><br><br /><br>PFS2, ORR, CBR based on local investigator*s assessment according to RECIST<br /><br>v1.1 in each cohort<br /><br><br /><br>Type, frequency and severity of adverse events per CTCAE v4.03<br /><br>Type, frequency and severity of laboratory toxicities per CTCAE v4.03</p><br>