Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant in Japanese Men and Postmenopausal Women With Advanced Breast Cancer

A Phase II Open-label, 2-Part, Multi-center Study of BYL719 (Alpelisib) in Combination With Fulvestrant for Men and Postmenopausal Women With PIK3CA Mutation Hormone Receptor (HR) Positive, HER2-negative, Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor (AI) Treatment in Japan Identifier: NCT04524000

Novartis Reference Number: CBYL719C1201

Last Update: Dec 19, 2020

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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

The purpose of this study is to assess the safety and efficacy of alpelisib plus fulvestrant in men and postmenopausal women with hormone receptor (HR) positive, human epidermal growth factor 2 (HER2)-negative, advanced breast cancer harboring a PIK3CA mutation in Japan, whose disease has progressed on or after aromatase inhibitor (AI) treatment regardless of prior CDK4/6 inhibitor use.

Advanced Breast Cancer
Phase 2
Overall status 
Enrollment count 
50 participants
Start date 
Nov 20, 2020
Completion date 
Feb 01, 2027
18 Years and older (Adult, Older Adult)


[Part 1] Alpelisib administered at 200 mg (DL 1), 250 mg (DL 2) or 300mg (DL 3) orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle. If DL 1 is tolerated, the alpelisib doses of 250 mg will be investigated. If DL 2 is tolerated, the alpelisib doses of 300 mg will be investigated. [Part 2] In the Part 2, participants will be enrolled into Cohort 2 (CDK4/6 inhibitor naive) and Cohort 3 (CDK4/6 inhibitor pre-treated) in parallel and alpelisib will be administered at the recommended dose identified in Part 1.
Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).

Eligibility Criteria

Inclusion Criteria:

Japanese man or postmenopausal woman
Participant has adequate tumor tissue for the analysis of PIK3CA mutational status by a Novartis designated laboratory.
Participant has identified PIK3CA mutation (as determined by a Novartis designated laboratory)
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 (FISH, CISH or SISH) test is required by local laboratory testing
Participant has measurable disease, i.e., at least one measurable lesion as per RECIST 1.1
Participant has advanced breast cancer
Participant has ECOG performance status 0 or 1

Exclusion Criteria:

Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy per the investigator's best judgment
Participant has received prior treatment;
with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor for Cohort 1 and 3
with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR, AKT inhibitor or CDK 4/6 inhibitor for Cohort 2
Participant has a known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant
Participant with inflammatory breast cancer at screening
Participant is concurrently using other anti-cancer therapy
Participant has had surgery within 14 days prior to starting study drug or has not recovered from major side effects
Participant with an established diagnosis at screening of diabetes mellitus type I or not controlled type II (based on FPG and HbA1c)
Participant has currently documented pneumonitis /interstitial lung disease
History of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
Participant with unresolved osteonecrosis of the jaw
Participant has a history of severe cutaneous reactions

Other protocol-defined inclusion/exclusion criteria may apply

Study Locations

Novartis Investigative Site
Isehara, 259-1193
Novartis Investigative Site
Yokohama-city, 241-8515
Novartis Investigative Site
Osaka-city, 540-0006
Novartis Investigative Site
Koto ku, 135 8550


Novartis Pharmaceuticals

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