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

Novartis

Status and phase: Active, not recruiting; Phase 2

Conditions: Advanced Breast Cancer

Treatments: Drug: Alpelisib; Drug: Fulvestrant

Study type: Interventional

Funder types: Industry

Identifiers

NCT04524000

CBYL719C1201

Details and patient eligibility

About

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.

Full description

This is a Phase II open-label, 2-Part, multi-center study in Japan. The study will be conducted in two parts: Part 1 (Cohort 1) includes participants regardless of prior CDK4/6 inhibitor use and is designed to determine the recommended dose (RD), evaluate the tolerability and safety of alpelisib in combination with fulvestrant. Part 2 consists of 2 cohorts (the CDK4/6 inhibitor naive participants are in Cohort 2 and the CDK4/6 inhibitor pre-treated participants are in Cohort 3) which are designed to assess the efficacy and safety of alpelisib in combination with fulvestrant, will start once the RD of alpelisib is established.

Participants will be treated until disease progression, unacceptable toxicity, death or discontinuation from the study treatment for any other reason and will be followed for survival regardless of treatment discontinuation reason (except if consent is withdrawn or participant is lost to follow up).

Enrollment: 24 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

Cohort 1:CDK4/6 inhibitor naive or pre-treated (Part 1)

Experimental group

Description:

Participants regardless of prior CDK4/6 inhibitor will be treated at escalating doses (200 mg, 250 mg and 300 mg, orally) of BYL719 in combination with Fulvestrant (500 mg, intramuscular).

Treatment:

Drug: Fulvestrant

Drug: Alpelisib

Cohort 2: CDK4/6 inhibitor naive (Part 2)

Experimental group

Description:

Participants who are CDK4/6 inhibitor naive will be treated with BYL719 at the recommended dose identified in Part 1 in combination with Fulvestrant (500 mg, intramuscular).

Treatment:

Drug: Fulvestrant

Drug: Alpelisib

Cohort 3: CDK4/6 inhibitor pre-treated (Part 2)

Experimental group

Description:

Participants who are CDK4/6 inhibitor pre-treated will be treated with BYL719 at the recommended dose identified in Part 1 in combination with Fulvestrant (500 mg, intramuscular).

Treatment:

Drug: Fulvestrant

Drug: Alpelisib