Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant in Men and Postmenopausal Women With Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment. (SOLAR-1)

A Phase III Randomized Double-blind, Placebo Controlled Study of Alpelisib in Combination With Fulvestrant for Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment

To determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival compared to fulvestrant and placebo in men and postmenopausal women with hormone receptor positive (HR+), HER2-negative advanced breast cancer, who received prior treatment with an Aromatase Inhibitor either as (neo)adjuvant or for advanced disease.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Fulvestrant; Drug: Alpelisib; Drug: Alpelisib placebo

• Study Type: Interventional
• Enrollment (Actual): 572
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • La Rioja, Argentina, 5300
    • Novartis Investigative Site
  • Buenos Aires
    • Berazategui, Buenos Aires, Argentina, B1884BBF
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1125ABD
      • Novartis Investigative Site
  • Viedma
    • Rio Negro, Viedma, Argentina, 8500
      • Novartis Investigative Site
• Australia
  • New South Wales
    • Wahroonga, New South Wales, Australia, 2076
      • Novartis Investigative Site
  • Queensland
    • Wooloongabba, Queensland, Australia, 4102
      • Novartis Investigative Site
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • Novartis Investigative Site
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Novartis Investigative Site
• Austria
  • Linz, Austria, 4010
    • Novartis Investigative Site
  • Vienna, Austria, 1090
    • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1000
    • Novartis Investigative Site
  • Libramont, Belgium, 6800
    • Novartis Investigative Site
  • Ottignies, Belgium, 1340
    • Novartis Investigative Site
  • Verviers, Belgium, 4800
    • Novartis Investigative Site
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Novartis Investigative Site
  • Brussel
    • Jette, Brussel, Belgium, 1090
      • Novartis Investigative Site
  • Oost Vlaanderen
    • Sint Niklaas, Oost Vlaanderen, Belgium, 9100
      • Novartis Investigative Site
• Brazil
  • Sao Jose do Rio Preto, Brazil, 15090 000
    • Novartis Investigative Site
  • Sao Paulo, Brazil, 01236 030
    • Novartis Investigative Site
  • RN
    • Natal, RN, Brazil, 59075 740
      • Novartis Investigative Site
  • RS
    • Lajeado, RS, Brazil, 95900-000
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 04014-002
      • Novartis Investigative Site
• Bulgaria
  • Plovdiv, Bulgaria, 4004
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1756
    • Novartis Investigative Site
  • Varna, Bulgaria, 9010
    • Novartis Investigative Site
  • Varna, Bulgaria, 9002
    • Novartis Investigative Site
• Canada
  • Quebec, Canada, G1S 4L8
    • Novartis Investigative Site
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Novartis Investigative Site
  • Ontario
    • Cambridge, Ontario, Canada, N1R 3G2
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, KIH 7W9
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5B 1W8
      • Novartis Investigative Site
• Chile
  • Santiago, Chile, 8420383
    • Novartis Investigative Site
  • Vina del Mar, Chile, 2520612
    • Novartis Investigative Site
  • Araucania
    • Temuco, Araucania, Chile, 4810469
      • Novartis Investigative Site
• Czechia
  • Prague 8, Czechia, 180 00
    • Novartis Investigative Site
  • Czech Republic
    • Hradec Kralove, Czech Republic, Czechia, 500 05
      • Novartis Investigative Site
    • Praha 4, Czech Republic, Czechia, 140 46
      • Novartis Investigative Site
    • Zlin, Czech Republic, Czechia, 762 75
      • Novartis Investigative Site
• France
  • Angers 02, France, 49055
    • Novartis Investigative Site
  • Avignon, France, 84082
    • Novartis Investigative Site
  • Caen, France, 14021
    • Novartis Investigative Site
  • Clermont Ferrand, France, 63011
    • Novartis Investigative Site
  • Creteil, France, 94010
    • Novartis Investigative Site
  • La Roche sur Yon cedex 9, France, 85925
    • Novartis Investigative Site
  • Le Chesnay, France, 78157
    • Novartis Investigative Site
  • Levallois-Perret, France, 92309
    • Novartis Investigative Site
  • Lyon Cedex 08, France, 69373
    • Novartis Investigative Site
  • Montpellier, France, 34070
    • Novartis Investigative Site
  • Nimes, France, 30029
    • Novartis Investigative Site
  • Rouen, France, 76038
    • Novartis Investigative Site
  • Saint-Herblain Cédex, France, 44805
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Novartis Investigative Site
  • Villejuif Cedex, France, 94800
    • Novartis Investigative Site
  • Bouches Du Rhone
    • Marseille cedex 20, Bouches Du Rhone, France, 13915
      • Novartis Investigative Site
• Germany
  • Aschaffenburg, Germany, 63739
    • Novartis Investigative Site
  • Frankfurt, Germany, 60389
    • Novartis Investigative Site
  • Friedrichshafen, Germany, 88045
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Homburg, Germany, 66421
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Potsdam, Germany, 14467
    • Novartis Investigative Site
  • Rostock, Germany, 18059
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Velbert, Germany, 42551
    • Novartis Investigative Site
  • North Rhine-westphalia
    • Recklinghausen, North Rhine-westphalia, Germany, 45657
      • Novartis Investigative Site
  • Sachsen
    • Leipzig, Sachsen, Germany, 04277
      • Novartis Investigative Site
  • Schleswig-Holstein
    • Luebeck, Schleswig-Holstein, Germany, 23563
      • Novartis Investigative Site
• Greece
  • Athens, Greece, 18547
    • Novartis Investigative Site
  • Athens, Greece, 115 28
    • Novartis Investigative Site
  • GR
    • Thessaloniki, GR, Greece, 564 29
      • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H 1122
    • Novartis Investigative Site
  • Budapest, Hungary, 1134
    • Novartis Investigative Site
  • Nyiregyhaza, Hungary, 4400
    • Novartis Investigative Site
  • Szekszard, Hungary, 7100
    • Novartis Investigative Site
• India
  • Mumbai, India, 400 012
    • Novartis Investigative Site
  • Andhra Pradesh
    • Vijayawada, Andhra Pradesh, India, 520002
      • Novartis Investigative Site
  • Maharashtra
    • Nagpur - Maharashtra, Maharashtra, India, 440010
      • Novartis Investigative Site
• Israel
  • Beer-Sheva, Israel, 8457108
    • Novartis Investigative Site
  • Haifa, Israel, 3109601
    • Novartis Investigative Site
  • Petach Tikva, Israel, 4941492
    • Novartis Investigative Site
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
  • CH
    • Chieti, CH, Italy, 66100
      • Novartis Investigative Site
  • FC
    • Meldola, FC, Italy, 47014
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90127
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35100
      • Novartis Investigative Site
  • PI
    • Pontedera, PI, Italy, 56025
      • Novartis Investigative Site
  • PN
    • Aviano, PN, Italy, 33081
      • Novartis Investigative Site
  • PZ
    • Rionero in Vulture, PZ, Italy, 85028
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00155
      • Novartis Investigative Site
  • SS
    • Sassari, SS, Italy, 07100
      • Novartis Investigative Site
  • SV
    • Savona, SV, Italy, 17100
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
  • VR
    • Negrar, VR, Italy, 37024
      • Novartis Investigative Site
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 464 8681
      • Novartis Investigative Site
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • Novartis Investigative Site
  • Gunma
    • Maebashi city, Gunma, Japan, 371 8511
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo-city, Hokkaido, Japan, 003-0804
      • Novartis Investigative Site
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
      • Novartis Investigative Site
  • Kagoshima
    • Kagoshima-city, Kagoshima, Japan, 892-0833
      • Novartis Investigative Site
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 241-8515
      • Novartis Investigative Site
  • Kumamoto
    • Kumamoto City, Kumamoto, Japan, 860-8556
      • Novartis Investigative Site
  • Osaka
    • Osaka-city, Osaka, Japan, 540-0006
      • Novartis Investigative Site
    • Osaka-city, Osaka, Japan, 541-8567
      • Novartis Investigative Site
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Novartis Investigative Site
  • Tokyo
    • Chuo ku, Tokyo, Japan, 104-8560
      • Novartis Investigative Site
    • Minato ku, Tokyo, Japan, 105-8470
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 06351
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Gyeonggi Do
    • Bundang Gu, Gyeonggi Do, Korea, Republic of, 13620
      • Novartis Investigative Site
  • Korea
    • Gyeonggi do, Korea, Korea, Republic of, 10408
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 05505
      • Novartis Investigative Site
• Lebanon
  • Ashrafieh, Lebanon, 166830
    • Novartis Investigative Site
  • Beirut, Lebanon, 10999
    • Novartis Investigative Site
  • Saida, Lebanon, 652
    • Novartis Investigative Site
• Mexico
  • San Luis Potosi, Mexico, 78200
    • Novartis Investigative Site
  • Monterrey
    • Monterrey NL, Monterrey, Mexico, 64320
      • Novartis Investigative Site
• Netherlands
  • Terneuzen, Netherlands, 4535 PA
    • Novartis Investigative Site
  • CE
    • Venray, CE, Netherlands, 5801
      • Novartis Investigative Site
• Peru
  • Lima, Peru, LIMA 27
    • Novartis Investigative Site
  • Lima
    • San Borja, Lima, Peru, 41
      • Novartis Investigative Site
    • Surquillo, Lima, Peru, 34
      • Novartis Investigative Site
• Romania
  • Iasi, Romania, 700483
    • Novartis Investigative Site
  • Cluj
    • Floresti, Cluj, Romania, 407280
      • Novartis Investigative Site
  • Dolj
    • Craiova, Dolj, Romania, 200347
      • Novartis Investigative Site
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Novartis Investigative Site
  • Ryazan, Russian Federation, 390011
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 197758
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28050
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
  • Cadiz
    • Jerez, Cadiz, Spain, 11407
      • Novartis Investigative Site
  • Cataluna
    • Barcelona, Cataluna, Spain, 08024
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Alicante, Comunidad Valenciana, Spain, 03010
      • Novartis Investigative Site
    • Castellon, Comunidad Valenciana, Spain, 12002
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
  • Extremadura
    • Badajoz, Extremadura, Spain, 06080
      • Novartis Investigative Site
    • Caceres, Extremadura, Spain, 10003
      • Novartis Investigative Site
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain, 07120
      • Novartis Investigative Site
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Novartis Investigative Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Novartis Investigative Site
  • Santa Cruz De Tenerife
    • La Laguna, Santa Cruz De Tenerife, Spain, 38320
      • Novartis Investigative Site
• Sweden
  • Gavle, Sweden, SE-801 87
    • Novartis Investigative Site
  • Oerebro, Sweden, 70185
    • Novartis Investigative Site
  • Vasteras, Sweden, 721 89
    • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • THA
    • Bangkok, THA, Thailand, 10330
      • Novartis Investigative Site
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Novartis Investigative Site
  • London, United Kingdom, SE1 9RT
    • Novartis Investigative Site
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8DH
      • Novartis Investigative Site
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Centers Chandler 2
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic - Arizona
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • Duarte, California, United States, 91010 3000
      • City of Hope National Medical Center
    • La Jolla, California, United States, 92037
      • Scripps Clinic SC
    • San Diego, California, United States, 92120
      • Kaiser Permanente - California Southern
    • San Francisco, California, United States, 94115
      • University of California San Francisco
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists FL Cancer Specialists
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists-North SC
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center Rush Uni Medical Center
    • Evanston, Illinois, United States, 60201
      • NorthShore University Health System NorthShore University
    • Naperville, Illinois, United States, 60540
      • Edward Cancer Center SC
  • Indiana
    • Fort Wayne, Indiana, United States, 46815
      • Fort Wayne Medical Oncology/Hematology, Inc. Dept.of Fort Wayne Med Onc/Hem
  • Kansas
    • Topeka, Kansas, United States, 66606-169
      • St. Francis Health Comprehensive Cancer Center SC
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center SC-2
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Updated Regulatory
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic
  • Michigan
    • Owosso, Michigan, United States, 48867
      • Detroit Clinical Research Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Cancer Institute SC
  • Montana
    • Billings, Montana, United States, 59102
      • St Vincent Frontier Cancer Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey SC-2
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland Seidman Cancer Center SC
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • Good Samaritan Regional Medical Center Good Samaritan Reg Med Ctr
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604
      • Lancaster General Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Upstate SC-2
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer SC
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology SC-3
  • Texas
    • Dallas, Texas, United States, 75231
      • Texas Oncology PA Dallas Presbyterian Hospital SC-1
    • El Paso, Texas, United States, 79902
      • El Paso, Texas Oncology
    • San Antonio, Texas, United States, 78229
      • Mays Cancer Ctr Uthsa Mdacc InstituteForDrugDevelopment(4)
    • Tyler, Texas, United States, 75702
      • Texas Oncology Northeast Texas
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists SC
  • Washington
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Medical Center SC-2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• If female, patient is postmenopausal
• Patient has identified PIK3CA status

• Patients may be:

  • relapsed with documented evidence of progression while on (neo) adjuvant endocrine therapy or within 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease;
  • relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy and then subsequently; progressed with documented evidence of progression while on or after only one line of endocrine therapy for metastatic disease;
  • newly diagnosed advanced breast cancer, then relapsed with documented evidence of progression while on or after only one line of endocrine therapy
• Patient has recurrence or progression of disease during or after AI therapy (i.e.

letrozole, anastrozole, exemestane).

• Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive breast cancer by local laboratory and has HER2 negative breast cancer
• Patient has either measurable disease per RECIST 1.1 criteria OR at least one predominantly lytic bone lesion must be present
• Patient has adequate bone marrow function

Exclusion Criteria:

• Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment
• Patient has received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor (pre-treatment with CDK4/6 inhibitors is allowed)
• Patient with inflammatory breast cancer at screening
• Patients with Child pugh score B or C
• Patients with an established diagnosis of diabetes mellitus type I or not controlled type II
• Patient has Eastern Cooperative Oncology Group (ECOG) performance status 2 or more
• Patient with CNS involvement unless he/she is at least 4 weeks from prior therapy completion to starting the study treatment and has stable CNS tumor at time of screening and not receiving steroids and/or enzyme inducing ant-epileptic medications for brain metastases
• Patient has participated in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer
• Patient has a history of acute pancreatitis within 1 year of screening or a past medical history of chronic pancreatitis
• Patient who relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease

Other protocol-defined inclusion/esclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fulvestrant + alpelisib; Alpelisib (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle)	Drug: Fulvestrant; Other Names: Faslodex; Drug: Alpelisib
Placebo Comparator: fulvestrant + placebo; Placebo (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle)	Drug: Fulvestrant; Other Names: Faslodex; Drug: Alpelisib placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) Per Investigator Assessment in the PIK3CA Mutant Cohort	PFS, 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 via a local radiology assessment according to RECIST 1.1	Once approximately 243 PFS events in this cohort had been observed, up to 32 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) for Patients With PI3KCA Mutant Status	OS is defined as the time from date of randomization to date of death due to any cause.	Up to approximatly 59 months
Overall Response Rate (ORR)	ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1.	Up to approximatly 36 months
Time to Definitive Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status	Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)	Baseline, Up to approximatly 36 months
Safety and Tolerability of Alpelisib in Combination With Fulvestrant	Safety will be determined by type, frequency and severity of adverse events per CTCAEv4.03 and type, frequency and severity of laboratory toxicities per CTCAEv4.03. Patients will be followed up for the duration of the study.	Up to approximatly 37 months
Time to 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30	Composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized	Up to approximatly 36 months
Plasma Concentration-time Profile of Alpelisib Given in Combinatio With Fulvestrant and Appropriate Pharmacokinetics (PK) Parameters	Assessment of any potential impact of fulvestrant on the pharmacokinetics of alpelisib by collection of sparse and trough PK samples. PK parameters includes,but not limited to, Cmin, Cmax, t1/2, AUClast for alpelisib (and any relevant metabolites) and fulvestrant	Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8
PFS Based on Radiology Assessments and Using RECIST 1.1 Criteria	PFS in patients with PIK3CA mutant status and patients with PIK3CA non-mutant status as measured in ctDNA.	Baseline, Up to approximatly 36 months
Clinical Benefit Rate (CBR)	Clinical benefit rate is defined as the proportion of patients with a best overall response of CR or PR or SD or Non-CR/Non-PD lasting more than 24 weeks based on local investigator assessment.	Up to approximatly 36 months
Change in the Global Health Status/(QOL) Scale Score of the EORTC QLQ-C30	Composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized	Baseline, Up to approximatly 36 months
Summary Statistics of Fulvestrant and Alpelisib Plasma Concentrations	Assessment of any potential impact of fulvestrant on the pharmacokinetics of alpelisib by collection of sparse and trough PK samples.	Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2,4, 6, 8
PFS for Patients With PIK3CA Non-mutant Status	PFS based on local radiology assessments and using RECIST 1.1 criteria in the PIK3CA non-mutant cohort	Up to approximatly 36 months
OS for Patients With PIK3CA Non-mutant Status	OS is defined as the time from date of randomization to date of death due to any cause.	Up to approximatly 59 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Ciruelos EM, Rugo HS, Mayer IA, Levy C, Forget F, Delgado Mingorance JI, Safra T, Masuda N, Park YH, Juric D, Conte P, Campone M, Loibl S, Iwata H, Zhou X, Park J, Ridolfi A, Lorenzo I, Andre F. Patient-Reported Outcomes in Patients With PIK3CA-Mutated Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer From SOLAR-1. J Clin Oncol. 2021 Jun 20;39(18):2005-2015. doi: 10.1200/JCO.20.01139. Epub 2021 Mar 29.
• Andre F, Ciruelos EM, Juric D, Loibl S, Campone M, Mayer IA, Rubovszky G, Yamashita T, Kaufman B, Lu YS, Inoue K, Papai Z, Takahashi M, Ghaznawi F, Mills D, Kaper M, Miller M, Conte PF, Iwata H, Rugo HS. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. Ann Oncol. 2021 Feb;32(2):208-217. doi: 10.1016/j.annonc.2020.11.011. Epub 2020 Nov 25.
• Rugo HS, Andre F, Yamashita T, Cerda H, Toledano I, Stemmer SM, Jurado JC, Juric D, Mayer I, Ciruelos EM, Iwata H, Conte P, Campone M, Wilke C, Mills D, Lteif A, Miller M, Gaudenzi F, Loibl S. Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Ann Oncol. 2020 Aug;31(8):1001-1010. doi: 10.1016/j.annonc.2020.05.001. Epub 2020 May 13.
• Andre F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, Yamashita T, Lu YS, Inoue K, Takahashi M, Papai Z, Longin AS, Mills D, Wilke C, Hirawat S, Juric D; SOLAR-1 Study Group. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019 May 16;380(20):1929-1940. doi: 10.1056/NEJMoa1813904.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2015
• Primary Completion (Actual): June 12, 2018
• Study Completion (Actual): June 9, 2023

Study Registration Dates

• First Submitted: April 22, 2015
• First Submitted That Met QC Criteria: May 4, 2015
• First Posted (Estimated): May 7, 2015

Study Record Updates

• Last Update Posted (Actual): November 18, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Phase III; BYL719; neoplasms; HR+; postmenopausal; men; advanced breast cancer; aromatase inhibitor; ER+; PI3K; HER2-negative; fulvestrant; alpelisib; PgR+
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: CBYL719C2301; 2015-000340-42 (EudraCT 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

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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