Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer Who Have Progressed on or After Prior Treatments (BYLieve)

BYLieve: A Phase II, Multicenter, Open-label, Three-cohort, Non- Comparative Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole in Patients With PIK3CA Mutant, Hormone Receptor (HR) Positive, HER2-negative Advanced Breast Cancer (aBC), Who Have Progressed on or After Prior Treatments

This was a Phase II, multicenter, open-label, three-cohort, non-comparative study of alpelisib plus endocrine therapy (either fulvestrant or letrozole) in subjects (pre- and post-menopausal women and men) with HR-positive, HER2-negative aBC harboring PIK3CA mutation(s) in the tumor, whose disease had progressed on or after prior treatments.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Alpelisib; Drug: Fulvestrant; Drug: Goserelin; Drug: Leuprolide; Drug: Letrozole

Detailed Description

The study comprised two phases:

1. Core Phase: included a treatment phase for all subjects from first subject first treatment (FSFT) until disease progression, unacceptable toxicity, or death until 18 months post last subject first treatment (LSFT) + 1 month safety follow-up (total 19 months post LSFT), discontinuation from the study treatment for any other reason, or sponsor terminates the study. At the start of the Core Phase, subjects were assigned to Cohort A, Cohort B, or Cohort C based on previous therapy as follows:

   • Cohort A: alpelisib (300 mg oral QD) + fulvestrant (500 mg intramuscular (IM)) to subjects whose last prior treatment was a CDK4/6i plus any AI;
   • Cohort B: alpelisib (300 mg oral QD) + letrozole (2.5 mg oral QD) to subjects whose last prior treatment was a CDK4/6i plus fulvestrant;
   • Cohort C: alpelisib (300 mg oral QD)+ fulvestrant (500 mg IM) to subjects who failed prior AI based therapy and whose last prior treatment was systemic chemotherapy or endocrine therapy (as monotherapy or in combination with targeted treatment except CDK 4/6i + AI). Endocrine therapy included letrozole, fulvestrant and CDK 4/6 inhibitor plus fulvestrant.
2. Extension Phase: included a treatment phase starting at the end of the treatment Core Phase until last subject last visit(LSLV) (up to 36 months). Following the end of the Core Phase, subjects continuing to derive benefit from study treatment who were not eligible for Post-Study Drug Supply (PSDS) in their country based on local regulations were re-consented and transitioned to the Extension Phase. Subjects continued on their existing study treatment assigned in the Core Phase until disease progression/lack of clinical benefit or any other reason for which the subject may have been discontinued from study treatment. If PSDS became available for a subject, the subject was to be discontinued from the study and to access treatment via PSDS. When subjects discontinued treatment for any reason, the end of treatment visit was performed after discontinuation of the medication , followed by safety follow-up 30 days after last dose.

A total of 340 subjects were planned to be enrolled, with approximately 112 subjects in each cohort. In the Core Phase, 379 subjects were analyzed, with 127 subjects in Cohort A, 126 subjects in Cohort B, and 126 subjects in Cohort C. In the Extension Phase, 11 subjects were analyzed, with 1 subject in Cohort A and 10 subjects in Cohort C.

• Study Type: Interventional
• Enrollment (Actual): 383
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • La Rioja, Argentina, 5300
    • Novartis Investigative Site
  • Buenos Aires
    • CABA, Buenos Aires, Argentina, C1125ABD
      • Novartis Investigative Site
    • CABA, Buenos Aires, Argentina, C1426ANZ
      • Novartis Investigative Site
    • CABA, Buenos Aires, Argentina, C1118AAT
      • Novartis Investigative Site
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000DSV
      • Novartis Investigative Site
  • Sante Fe
    • Rosario, Sante Fe, Argentina, S200KZE
      • Novartis Investigative Site
• Belgium
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Liège, Belgium, 4000
    • Novartis Investigative Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Novartis Investigative Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Novartis Investigative Site
  • Ontario
    • Kitchener, Ontario, Canada, N2G 1G3
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5B 1N9
      • Novartis Investigative Site
• Chile
  • Santiago, Chile, 8420383
    • Novartis Investigative Site
  • Santiago, Chile, 7500921
    • Novartis Investigative Site
  • Región de la Araucanía
    • Temuco, Región de la Araucanía, Chile, 4810469
      • Novartis Investigative Site
• Denmark
  • Odense C, Denmark, 5000
    • Novartis Investigative Site
  • Vejle, Denmark, DK-7100
    • Novartis Investigative Site
• France
  • Bordeaux, France, 33076
    • Novartis Investigative Site
  • Caen, France, 14021
    • Novartis Investigative Site
  • Lille, France, 59020
    • Novartis Investigative Site
  • Lyon, France, 69373
    • Novartis Investigative Site
  • Montpellier, France, 34298
    • Novartis Investigative Site
  • Saint-Herblain, France, 44805
    • Novartis Investigative Site
  • Strasbourg, France, 67000
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Novartis Investigative Site
  • Alpes Maritimes
    • Nice, Alpes Maritimes, France, 06189
      • Novartis Investigative Site
  • Hauts De Seine
    • Saint-Cloud, Hauts De Seine, France, 92210
      • Novartis Investigative Site
• Germany
  • Augsburg, Germany, 86150
    • Novartis Investigative Site
  • Berlin, Germany, 14169
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Essen, Germany, 45136
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Novartis Investigative Site
• India
  • Delhi, India, 110085
    • Novartis Investigative Site
• Israel
  • Petah Tikva, Israel, 4941492
    • Novartis Investigative Site
  • Ramat Gan, Israel, 5265601
    • Novartis Investigative Site
  • Rehovot, Israel, 7661041
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
  • BG
    • Bergamo, BG, Italy, 24127
      • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16132
      • Novartis Investigative Site
  • MI
    • Milan, MI, Italy, 20133
      • Novartis Investigative Site
    • Milan, MI, Italy, 20141
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
• Japan
  • Osaka
    • Osaka, Osaka, Japan, 540-0006
      • Novartis Investigative Site
• Mexico
  • Jalisco, Mexico, 45640
    • Novartis Investigative Site
• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 217562
    • Novartis Investigative Site
  • Singapore, Singapore, 168583
    • Novartis Investigative Site
• South Korea
  • Seoul, South Korea, 06351
    • Novartis Investigative Site
  • Korea
    • Seoul, Korea, South Korea, 03080
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08036
    • Novartis Investigative Site
  • Castellon, Spain, 12002
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Seville, Spain, 41013
    • Novartis Investigative Site
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Novartis Investigative Site
  • Castille and León
    • Salamanca, Castille and León, Spain, 37007
      • Novartis Investigative Site
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Novartis Investigative Site
• Taiwan
  • Tainan, Taiwan, 70403
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 103616
    • Novartis Investigative Site
• United Kingdom
  • Leicester, United Kingdom, LE2 7LG
    • Novartis Investigative Site
  • London, United Kingdom, SW3 6JJ
    • Novartis Investigative Site
  • Nottingham, United Kingdom, NG5 1PB
    • Novartis Investigative Site
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Novartis Investigative Site
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Novartis Investigative Site
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • California
    • Anaheim, California, United States, 92807
      • Kaiser Permanente Medical Group
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • Irvine, California, United States, 92660
      • University of Calif Irvine Med Cntr
    • San Diego, California, United States, 92120
      • Kaiser Permanent Southern Californi
    • San Francisco, California, United States, 94115
      • UCSF
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University Yale Cancer Center
  • Florida
    • Orlando, Florida, United States, 32804
      • Advent Health Cancer Institute
  • Kansas
    • Kansas City, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville James Graham Brown Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Med Center Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center
  • Montana
    • Billings, Montana, United States, 59102
      • St Vincent Frontier Cancer Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • New Mexico Cancer Care Alliance
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloane Ketterin Cancer Ctr
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Uni Hosp of Cleveland Cancer Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio
    • San Antonio, Texas, United States, 78229
      • Cancer Care Centers of South Texas HOAST
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria: Subjects eligible for inclusion in the Core Phase of the study fulfilled the following key inclusion criteria:

• Subject was an adult male or female ≥ 18 years of age.
• Subjects with histologically and/or cytologically confirmed diagnosis of estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive breast cancer by local laboratory.
• Subjects with a confirmed human epidermal growth factor receptor-2 (HER2)-negative aBC.
• Subjects with gene encoding the p110alpha catalytic subunit of PI3K (phosphatidylinositol-3-kinase) (PIK3CA) mutation.
• In case of women, both premenopausal and postmenopausal subjects were allowed to be included in this study.

• Subjects with documented evidence of tumor progression on or after:

  i. Cyclin-Dependent Kinase 4 and 6 inhibitor (CDK4/6i) treatment as last treatment regimen in Cohorts A and B.

ii. aromatase inhibitor (AI) treatment (either in adjuvant or metastatic setting) and received systemic chemotherapy or ET (monotherapy or combination except CDK4/6i + AI) as last treatment regimen in Cohort C. Upon completion of enrollment of Cohort B, subjects who received CDK4/6i + fulvestrant as immediate prior therapy were eligible for Cohort C.

iii. No more than 2 prior anticancer therapies for aBC. iv. Received no more than 1 prior regimen of chemotherapy for the treatment of advanced/metastatic disease was permitted.

v. Recovered to grade 1 or better from any adverse events (AEs) related to previous anticancer therapy prior to study entry (except alopecia or other toxicities not considered a safety risk for the subject at the investigator's discretion).

• Subjects with:

  i. Measurable disease, i.e., at least 1 measurable lesion as per RECIST v1.1 criteria; or ii. If no measurable disease was present, at least 1 predominantly lytic bone lesion had to be present.

• Subjects with adequate bone marrow and coagulation function, liver function and renal function as shown by laboratory values.
• Subjects with Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.

Key exclusion criteria were:

• Subjects with a known hypersensitivity to alpelisib, fulvestrant, letrozole, goserelin, or leuprolide or to any of their excipients.
• Subjects with prior treatment with any PI3K inhibitor (PI3Ki).

• Subjects with central nervous system (CNS) involvement unless they met all of the following criteria:

  i. At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment, ii. Clinically stable CNS tumor at the time of screening untreated or without evidence of progressions for at least 4 weeks after treatment as determined by clinical examination and brain imaging (magnetic resonance imaging (MRI) or computed tomography (CT) during screening period and stable low dose of steroids for 2 weeks prior to initiating study treatment.

• Subjects with an established diagnosis of diabetes mellitus type I or uncontrolled type II.
• Any concurrent severe and/or uncontrolled medical conditions that would, in the investigator's judgment, contraindicate subject participation in the study (e.g., chronic active hepatitis, severe hepatic impairment, etc.).
• Subjects with a history of noncompliance to medical regimens.
• Subjects with impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of the study drugs based on investigator discretion.
• Subjects with documented pneumonitis/interstitial lung disease which was active and requiring treatment.
• Subjects concurrently using other anticancer therapy. All anticancer therapy had to be discontinued prior to Day 1 of study treatment.
• Subjects who had major surgery within 14 days prior to starting treatment with alpelisib, or did not recover from major side effects.
• Subjects with significant cardiac abnormalities.
• History of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis.
• Subjects who did not use highly effective contraception while on alpelisib and through the duration after the final dose of alpelisib (not applicable to postmenopausal women).
• Subjects with unresolved osteonecrosis of the jaw.

Other inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Pre-treated with CDK 4/6i + AI; Participants who received any Cyclin-Dependent Kinases 4 and 6 inhibitor (CDK 4/6i) plus aromatase inhibitor (AI) as immediate prior treatment will receive alpelisib + fulvestrant	Drug: Alpelisib; 300 mg of alpelisib film-coated tablets administered orally once daily; Other Names: BYL719; Drug: Fulvestrant; 500 mg of fulvestrant via intramuscular injection administered on Days 1, 15 on Cycle 1 and Day 1 at each cycle thereafter. Cycle=28 days; Drug: Goserelin; 3.6 mg of goserelin via injectable subcutaneous implant administered every 28 days. Only for men in Cohort B and premenopausal women.; Drug: Leuprolide; 7.5 mg of leuprolide via injectable intramuscular depot administered every 28 days. Only for men in cohort B and premenopausal women.
Experimental: Cohort B: Pre-treated with CDK 4/6i + fulvestrant; Patients who received any CDK 4/6i plus fulvestrant as immediate prior treatment will receive alpelisib + letrozole	Drug: Alpelisib; 300 mg of alpelisib film-coated tablets administered orally once daily; Other Names: BYL719; Drug: Goserelin; 3.6 mg of goserelin via injectable subcutaneous implant administered every 28 days. Only for men in Cohort B and premenopausal women.; Drug: Leuprolide; 7.5 mg of leuprolide via injectable intramuscular depot administered every 28 days. Only for men in cohort B and premenopausal women.; Drug: Letrozole; 2.5 mg of letrozole film-coated tablets administered orally once daily
Experimental: Cohort C: Pre-treated with systemic chemotherapy or ET; Participants who received systemic chemotherapy or endocrine therapy (ET) (as monotherapy or in combination with targeted treatment except CDK 4/6i + AI) as immediate prior treatment will receive alpelisib + fulvestrant.	Drug: Alpelisib; 300 mg of alpelisib film-coated tablets administered orally once daily; Other Names: BYL719; Drug: Fulvestrant; 500 mg of fulvestrant via intramuscular injection administered on Days 1, 15 on Cycle 1 and Day 1 at each cycle thereafter. Cycle=28 days; Drug: Goserelin; 3.6 mg of goserelin via injectable subcutaneous implant administered every 28 days. Only for men in Cohort B and premenopausal women.; Drug: Leuprolide; 7.5 mg of leuprolide via injectable intramuscular depot administered every 28 days. Only for men in cohort B and premenopausal women.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Phase: Percentage of Participants Who Were Alive Without Disease Progression at 6 Months	Percentage of participants who were alive without disease progression at 6-month follow-up based on local investigator assessment per RECIST v1.1 in Cohort A, Cohort B and Cohort C. Participants who progressed, died, or discontinued study before 6 months were counted as a failure.	At 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Phase: Overall Survival (OS)	OS is defined as the time of start of treatment to date of death or lost to follow-up. If a subject was not known to have died, then the OS data was censored at the date of the last known alive status for the patient.	From date of first dose and up to approximately 55 months
Core Phase: Progression Free Survival (PFS)	PFS is defined as the time from the date of first dose of study medication to the date of the first documented progression or death due to any cause occurring in the study. PFS was assessed based on local investigator's assessment according to RECIST v1.1. PFS was censored if no PFS event was observed before the cut-off date. The censoring date was the date of last adequate tumor assessment before the cut-off date. If a PFS event was observed after two or more missing or non-adequate tumor assessments, then PFS was censored at the last adequate tumor assessment. PFS was estimated using the Kaplan-Meier method.	From date of first dose to date of first documented progression or death, up to 46 months
Core Phase: Progression Free Survival on Next Line Treatment (PFS2)	PFS2 is defined as time from the date of first dose of study medication to the date of first documented progression on next-line therapy or death from any cause. The first documented progression on next-line treatment is based on investigator assessment of progressive disease. PFS2 was estimated using the Kaplan-Meier method.	From date of first dose to date of first documented progression on next-line therapy or death, up to approximately 55 months
Core Phase: Overall Response Rate (ORR)	ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST v1.1 in each cohort. CR: Disappearance of all non-nodal target lesions and all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm and all lymph nodes assigned as non-target lesions must be non-pathological in size (<10 mm short axis) PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.	Up to 46 months
Core Phase: Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with a BOR of CR or PR or an overall lesion response of stable disease (SD) or Non-CR/ Non-PD lasting ≥ 24 weeks based on local investigator's assessment according to RECIST v1.1. CR: Disappearance of all non-nodal target lesions and all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm and all lymph nodes assigned as non-target lesions must be non-pathological in size (<10 mm short axis) PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.	Up to 46 months
Core Phase: Duration of Response (DOR)	DOR is the time from the date of first documented response (confirmed CR or PR based on local investigator's assessment according to RECIST v1.1) to the date of first documented progression or death due to underlying cancer. Subjects continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment. DOR was estimated using the Kaplan-Meier method.	From date of first documented response to first documented progression or death, up to 33.3 months
Extension Phase: Percentage of Participants With Clinical Benefit as Assessed by the Investigator During the Extension Phase	Clinical Benefit Rate, as assessed by the Investigator during the Extension Phase, was defined as the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR), or an overall lesion response of Stable Disease (SD) or non-complete response/non-progressive disease that lasted at least 24 weeks, based on the local investigator's assessment according to Response Evaluation Criteria in Solid Tumors version 1.1.	Day 1 of each extension cycle up to Cycle 29 (each cycle lasting 28 days); median duration of exposure to study treatment (alpelisib or fulvestrant) = 41 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Rugo HS, Lerebours F, Ciruelos E, Drullinsky P, Ruiz-Borrego M, Neven P, Park YH, Prat A, Bachelot T, Juric D, Turner N, Sophos N, Zarate JP, Arce C, Shen YM, Turner S, Kanakamedala H, Hsu WC, Chia S. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2021 Apr;22(4):489-498. doi: 10.1016/S1470-2045(21)00034-6. Erratum In: Lancet Oncol. 2021 May;22(5):e184. doi: 10.1016/S1470-2045(21)00194-7.
• Rugo HS, Lerebours F, Ciruelos E, Drullinsky P, Ruiz-Borrego M, Neven P, Park YH, Prat A, Bachelot T, Juric D, Turner N, Sophos N, Zarate JP, Arce C, Shen YM, Turner S, Kanakamedala H, Hsu WC, Chia S. Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study. Lancet Oncol. 2024 Dec;25(12):e629-e638. doi: 10.1016/S1470-2045(24)00673-9.
• Borrego MR, Lu YS, Reyes-Cosmelli F, Park YH, Yamashita T, Chiu J, Airoldi M, Turner N, Fein L, Ghaznawi F, Singh J, Pantoja K, Schnell C, Akdere M, Chia S. SGLT2 inhibition improves PI3Kalpha inhibitor-induced hyperglycemia: findings from preclinical animal models and from patients in the BYLieve and SOLAR-1 trials. Breast Cancer Res Treat. 2024 Nov;208(1):111-121. doi: 10.1007/s10549-024-07405-8. Epub 2024 Aug 23.
• Rodon J, Demanse D, Rugo HS, Burris HA, Simo R, Farooki A, Wellons MF, Andre F, Hu H, Vuina D, Quadt C, Juric D. A risk analysis of alpelisib-induced hyperglycemia in patients with advanced solid tumors and breast cancer. Breast Cancer Res. 2024 Mar 4;26(1):36. doi: 10.1186/s13058-024-01773-1.

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2017
• Primary Completion (Actual): June 14, 2021
• Study Completion (Actual): November 12, 2024

Study Registration Dates

• First Submitted: February 15, 2017
• First Submitted That Met QC Criteria: February 15, 2017
• First Posted (Actual): February 17, 2017

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: PIK3CA; HR+; AI; advanced breast cancer; letrozole; aromatase inhibitor; CDK 4/6 inhibitor; HER2-negative; pre-menopausal; fulvestrant; post menopausal; endocrine treatment; ET
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Skin Diseases; Breast Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Breast Neoplasms; Hereditary Sensory and Autonomic Neuropathies; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Nitriles; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Triazoles; Gonadotropin-Releasing Hormone; Letrozole; Fulvestrant; Leuprolide; Goserelin; Alpelisib
• Other Study ID Numbers: CBYL719X2402; 2023-509167-24-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No