Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant in Participants With HR-positive (HR+), HER2-negative, Advanced Breast Cancer After Treatment With a CDK4/6 Inhibitor and an Aromatase Inhibitor.

NCT05038735 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: CBYL719C23032023-509133-39-00
• Study Type: interventional
• Target: 234
• Locations: 17 countries
• Sites: 68

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Alpelisib; Fulvestrant; Advanced breast cancer; Phase III; HR-positive; HER-2 negative; CDK4/6 inhibitor; PIK3CA mutation; Progression free survival; aromatase inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) based on BIRC assessments and using RECIST v1.1 criteria

  Progression-free survival (PFS) is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed by the Blinded Independent Review Committee (BIRC) according to RECIST 1.1.

  From randomization to date of the first documented progression or death due to any cause, assessed up to a maximum duration of 60 months.

Secondary Outcomes (10)

• Overall survival (OS)

  From the date of randomization to the date of death up to a maximum duration of 60 months

• Overall response rate (ORR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria

  From the date of randomization up to a maximum duration of 60 months

• Clinical benefit rate (CBR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria

  From the date of randomization up to a maximum duration of 60 months

• Duration of response (DOR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria

  From first documented response to the date of first progression or deaths, up to a maximum duration of 60 months

• Time to response (TTR) based on BIRC assessments and using RECIST v1.1 criteria

  From the date of randomization to the first documented response up to a maximum duration of 60 months

Study Arms (2)

Alpelisib plus fulvestrant

EXPERIMENTAL

Alpelisib 300 mg orally once daily on a continuous dosing schedule, in a 28-day cycle + fulvestrant 500 mg as intramuscular injection on Cycle 1 Day 1 and 15, and on Day 1 on every Cycle thereafter, in a 28 days cycle.

Drug: Alpelisib; Drug: Fulvestrant

Alpelisib-matching placebo plus fulvestrant

PLACEBO COMPARATOR

Alpelisib-matching placebo orally once daily on a continuous dosing schedule, in a 28-day cycle + fulvestrant 500 mg as intramuscular injection on Cycle 1 Day 1 and 15 and on Day 1 on every Cycle thereafter, in a 28 days cycle. After Protocol Amendment 5 is implemented, alpelisib matching-placebo will no longer be supplied or administered once participants have been unblinded.

Drug: Fulvestrant; Drug: Alpelisib-matching placebo

Interventions

Alpelisib DRUG

Alpelisib (tablets) administered at 300mg orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

Alpelisib plus fulvestrant

Fulvestrant DRUG

Fulvestrant (prefilled syringe) 500mg administered intramuscularly at Cycle 1 Day 1 and 15 and then at Day 1 of each subsequent cycle (each cycle is 28 days).

Alpelisib plus fulvestrant; Alpelisib-matching placebo plus fulvestrant

Alpelisib-matching placebo DRUG

Alpelisib-matching placebo (tablets) administered orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle. After Protocol Amendment 5 is implemented, alpelisib matching-placebo will no longer be supplied or administered once participants have been unblinded.

Alpelisib-matching placebo plus fulvestrant

Eligibility Criteria

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

You may qualify if:

• 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.
• 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) is permitted.
• The presence of PIK3CA mutation(s) determined in tumor tissue prior to 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.
• If female, then the participant must be in postmenopausal status.

You may not qualify if:

• Participant with symptomatic visceral disease or any disease burden 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 (SERD), any Phosphatidylinositol-3-Kinase (PI3K), mammalian Target of Rapamycin (mTOR) or Protein Kinase B (AKT) inhibitor.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (68)

Novartis Investigative Site

Sint-Niklaas, Oost Vlaanderen, 9100, Belgium

Location

Novartis Investigative Site

Brussels, 1000, Belgium

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Liège, 4000, Belgium

Location

Novartis Investigative Site

Plovdiv, 4004, Bulgaria

Location

Novartis Investigative Site

Sofia, 1330, Bulgaria

Location

Novartis Investigative Site

Calgary, Alberta, T2N 5G2, Canada

Location

Novartis Investigative Site

Ottawa, Ontario, K1H 8L6, Canada

Location

Novartis Investigative Site

Brno, 656 53, Czechia

Location

Novartis Investigative Site

Nový Jičín, 741 01, Czechia

Location

Novartis Investigative Site

Prague, 100 34, Czechia

Location

Novartis Investigative Site

Prague, 128 08, Czechia

Location

Novartis Investigative Site

Prague, 140 59, Czechia

Location

Novartis Investigative Site

Aalborg, 9000, Denmark

Location

Novartis Investigative Site

Helsinki, 00029, Finland

Location

Novartis Investigative Site

Tampere, FIN-33521, Finland

Location

Novartis Investigative Site

Besançon, 25030, France

Location

Novartis Investigative Site

Clermont-Ferrand, 63011, France

Location

Novartis Investigative Site

La Roche-sur-Yon, 85925, France

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Marseille, 13273, France

Location

Novartis Investigative Site

Montpellier, 34298, France

Location

Novartis Investigative Site

Paris, 75475, France

Location

Novartis Investigative Site

Paris, 75970, France

Location

Novartis Investigative Site

Valenciennes, 59300, France

Location

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Novartis Investigative Site

Augsburg, 86150, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Essen, 45136, Germany

Location

Novartis Investigative Site

Lübeck, 23538, Germany

Location

Novartis Investigative Site

Athens, 115 22, Greece

Location

Novartis Investigative Site

Pátrai, 265 04, Greece

Location

Novartis Investigative Site

Budapest, H 1122, Hungary

Location

Novartis Investigative Site

Dublin, DO4, Ireland

Location

Novartis Investigative Site

Bari, BA, 70124, Italy

Location

Novartis Investigative Site

Bergamo, BG, 24127, Italy

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Florence, FI, 50134, Italy

Location

Novartis Investigative Site

Genova, GE, 16132, Italy

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Palermo, PA, 90127, Italy

Location

Novartis Investigative Site

Padova, PD, 35128, Italy

Location

Novartis Investigative Site

Aviano, PN, 33081, Italy

Location

Novartis Investigative Site

Roma, RM, 00168, Italy

Location

Novartis Investigative Site

Terni, TR, 05100, Italy

Location

Novartis Investigative Site

Milan, 20141, Italy

Location

Novartis Investigative Site

Naples, 80131, Italy

Location

Novartis Investigative Site

Bydgoszcz, 85 796, Poland

Location

Novartis Investigative Site

Coimbra, 3000-075, Portugal

Location

Novartis Investigative Site

Lisbon, 1099-023, Portugal

Location

Novartis Investigative Site

Lisbon, 1400-038, Portugal

Location

Novartis Investigative Site

Porto, 4200-072, Portugal

Location

Novartis Investigative Site

Floreşti, Cluj, 407280, Romania

Location

Novartis Investigative Site

Bratislava, 812 50, Slovakia

Location

Novartis Investigative Site

Bratislava, 83310, Slovakia

Location

Novartis Investigative Site

Košice, 041 91, Slovakia

Location

Novartis Investigative Site

Badajoz, Extremadura, 06080, Spain

Location

Novartis Investigative Site

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Novartis Investigative Site

Oviedo, Principality of Asturias, 33011, Spain

Location

Novartis Investigative Site

A Coruña, 15009, Spain

Location

Novartis Investigative Site

Barcelona, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Málaga, 29011, Spain

Location

Novartis Investigative Site

Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Alpelisib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

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 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: September 9, 2021
• Study Start: December 17, 2021
• Primary Completion (Estimated): January 28, 2027
• Study Completion (Estimated): February 26, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

HU (1); BE (6); BU (2); IE (1); RO (1); DE (5); DK (1); PT (4); IT (15); PL (1); SL (3); CA (2); FI (2); FR (9); GR (2); CZ (5); ES (8)