Study Description
The purpose of this study is to complement Study CBYL719C2301 (SOLAR-1) and obtain more
comprehensive data on the efficacy and safety of alpelisib (BYL719) in combination with
fulvestrant compared with placebo plus fulvestrant in men or postmenopausal women with
HR-positive, HER2-negative advanced breast cancer with a PIK3CA mutation who progressed
or relapsed on or after treatment with an AI plus a CDK4/6 inhibitor. This is a Phase III, randomized, double-blind, placebo-controlled, international,
multi-center trial. Approximately 234 men and postmenopausal women will be randomized to
either alpelisib plus fulvestrant or alpelisib-matching placebo plus fulvestrant.
Randomization will follow a 1:1 randomization ratio and be stratified by presence of lung
and/or liver metastases (yes vs. no) and setting at last prior CDK4/6 inhibitor therapy
(adjuvant vs metastatic).
Study treatment with alpelisib plus fulvestrant or alpelisib-matching placebo plus
fulvestrant will be initiated on Cycle 1 Day 1, and will continue until disease
progression per RECIST v1.1 as per BIRC assessment, start of new antineoplastic therapy,
death, lost to follow-up, or withdrawal of consent. A cycle is defined as 28 days.
Participants randomized to the alpelisib-matching placebo plus fulvestrant arm who have
disease progression per RECIST v1.1 as assessed by BIRC will have the option to crossover
to be treated with alpelisib plus fulvestrant.
Unblinding a single participant at a site will be permitted after disease progression
confirmed by BIRC after discussion with the Novartis team to determine eligibility for
cross-over to treatment with alpelisib plus fulvestrant.
Interventions
Alpelisib
Alpelisib-matching placebo
Fulvestrant
Eligibility Criteria
Inclusion Criteria:
- Participant is an adult ≥ 18 years old at the time of informed consent and has
signed informed consent before any trial related activities and according to local
guidelines.
- If female, then the participant must be in postmenopausal status. Postmenopausal
status is defined either by: prior bilateral oophorectomy, age ≥60 or age <60 and
amenorrheic for 12 or more months in the absence of chemotherapy, tamoxifen,
toremifene, or ovarian suppression and follicle-stimulating hormone (FSH) and
estradiol in the postmenopausal range per local normal range.
- Participant has a histologically and/or cytologically confirmed diagnosis of ER+
and/or PgR+ breast cancer by local laboratory.
- Participant has HER2-negative breast cancer defined as a negative in situ
hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ
hybridization (Fluorescent in situ hybridization (FISH), Chromogenic in situ
hybridization (CISH), or Silver-enhanced in situ hybridization (SISH)) test is
required by local laboratory testing.
- Participant has at least one measurable lesion as per RECIST v1.1 criteria as
assessed by Investigator (a lesion at a previously irradiated site may only be
counted as a target lesion if there is clear sign of progression since the
irradiation).
- Participant has recurrence or progression of disease during or after combined AI
(i.e. letrozole, anastrozole, exemestane) and CDK4/6 inhibitor therapy. The combined
AI and CDK4/6 inhibitor therapy does not need to be the latest treatment regimen
(including adjuvant setting).
- Participant has received ≤2 prior lines of systemic therapies overall in the
metastatic setting, of which a maximum of 1 line of prior treatment with
chemotherapy (except for neoadjuvant/ adjuvant chemotherapy).
- Participant must show the presence of a PIK3CA mutation(s) determined in tumor
tissue prior ro enrollment either by a Novartis designated laboratory or in tumor
tissue or plasma ctDNA by a local laboratory using a Food and Drug Administration
(FDA)-approved PIK3CA Companion Diagnostics (CDx) test for alpelisib or the CE-IVD
QIAGEN Therascreen® PIK3CA RGQ PCR test.
Exclusion Criteria:
- Participant with symptomatic visceral disease that makes the participant ineligible
for endocrine therapy (ET) per the investigator's best judgment.
- Participant who relapsed with documented evidence of progression more than 12 months
from completion of (neo)adjuvant endocrine/endocrine-based therapy with no treatment
for metastatic disease
- Participant has received prior treatment with fulvestrant, any oral selective
estrogen receptor degrader (SERDs), any Phosphatidylinositol-3-Kinase (PI3K),
mammalian Target of Rapamycin (mTOR) or Protein Kinase B (AKT) inhibitor
Other Inclusion and Exclusion Criteria do apply
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Praha,12808,Czechia
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