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

NCT04524000 | Active Not Recruiting Phase 2

• 1 other identifier: CBYL719C1201
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Advanced Breast Cancer

Keywords

HR+; HER2-negative; PIK3CA mutation; Advanced breast cancer; Alpelisib; Fulvestrant; open-label; Part 1; Part 2; Japanese population

Outcome Measures

Primary Outcomes (2)

• [Part 1] The incidence of Dose Limiting Toxicities (DLTs) of alpelisib in combination with fulvestrant

  A DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 2 cycles (the first 56 days) of treatment with alpelisib in combination with fulvestrant and meets any of the criteria specified in the protocol .

  From Cycle 1 Day 1 to Cycle 2 Day 28 (Cycle = 28 days)

• [Part 2] Overall Response Rate (ORR) in CDK4/6 inhibitor naive participants

  ORR is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on local investigator assessment per RECIST 1.1.

  Up to approximately 36 months

Secondary Outcomes (17)

• [Part 1] Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to approximately 37 months

• [Part 1] Number of participants with dose adjustments

  Up to approximately 37 months

• [Part 1] Dose intensity for alpelisib and fulvestrant

  Up to approximately 37 months

• [Part 1] Duration of exposure for alpelisib and fulvestrant

  Up to approximately 37 months

• [Part 1] Plasma concentrations of alpelisib in combination with fulvestrant

  Cycle 1 Day 8 (pre-dose), 15 (pre-dose, post-dose 1 hour, 3 hours) and Day 1 of Cycles 2, 4, 6, 8 (pre-dose) (Cycle = 28 days)

Study Arms (3)

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

EXPERIMENTAL

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).

Drug: Alpelisib; Drug: Fulvestrant

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

EXPERIMENTAL

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).

Drug: Alpelisib; Drug: Fulvestrant

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

EXPERIMENTAL

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).

Drug: Alpelisib; Drug: Fulvestrant

Interventions

Alpelisib DRUG

\[Part 1\] 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.

Also known as: BYL719

Cohort 1:CDK4/6 inhibitor naive or pre-treated (Part 1); Cohort 2: CDK4/6 inhibitor naive (Part 2); Cohort 3: CDK4/6 inhibitor pre-treated (Part 2)

Fulvestrant DRUG

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).

Also known as: Faslodex

Cohort 1:CDK4/6 inhibitor naive or pre-treated (Part 1); Cohort 2: CDK4/6 inhibitor naive (Part 2); Cohort 3: CDK4/6 inhibitor pre-treated (Part 2)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Novartis Investigative Site

Nagoya, Aichi-ken, 464 8681, Japan

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 4668560, Japan

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 4678602, Japan

Location

Novartis Investigative Site

Kashiwa, Chiba, 277-8577, Japan

Location

Novartis Investigative Site

Isehara, Kanagawa, 259-1193, Japan

Location

Novartis Investigative Site

Yokohama, Kanagawa, 241-8515, Japan

Location

Novartis Investigative Site

Sendai, Miyagi, 9808574, Japan

Location

Novartis Investigative Site

Osaka, Osaka, 5400006, Japan

Location

Novartis Investigative Site

Osaka, Osaka, 5418567, Japan

Location

Novartis Investigative Site

Suita, Osaka, 565-0871, Japan

Location

Novartis Investigative Site

Bunkyo Ku, Tokyo, 1138677, Japan

Location

Novartis Investigative Site

Koto Ku, Tokyo, 135-8550, Japan

Location

Novartis Investigative Site

Meguro-ku, Tokyo, 152-8902, Japan

Location

Novartis Investigative Site

Kumamoto, 860-8556, Japan

Location

Novartis Investigative Site

Niigata, 951-8566, Japan

Location

MeSH Terms

Interventions

Alpelisib; Fulvestrant

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 of the study has a "Single group" design and the Part 2 has a "Parallel" design.

Study Record Dates

• First Submitted: August 19, 2020
• First Posted: August 24, 2020
• Study Start: January 8, 2021
• Primary Completion (Estimated): February 26, 2027
• Study Completion (Estimated): February 27, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

JP (15)