Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/HER2- Breast Cancer (VIKTORIA-1)

Breast Cancer Clinical Trial

— VIKTORIA-1  

Official title:

Phase 3, Open-Label, Randomized, Study Comparing Gedatolisib Combined With Fulvestrant & With or Without Palbociclib to Standard-of-Care Therapies in Patients With HR-Positive, HER2-Negative Advanced Breast Cancer Previously Treated With a CDK4/6 Inhibitor in Combination w/Non-Steroidal Aromatase Inhibitor Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05501886
• Other study ID #: CELC-G-301
• Secondary ID: 2021-005235-24
• Status: Recruiting
• Phase: Phase 3
• Start date: September 30, 2022
• Est. completion date: September 30, 2026

Study information

• Verified date: July 2023
• Source: Celcuity, Inc.
• Contact: Nadene Zack, MS
• Phone: 844-310-3900
• Email: VIKTORIA-1_TRIAL[@]CELCUITY.COM
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 3, open-label, randomized, clinical trial evaluating the efficacy and safety of gedatolisib plus fulvestrant with or without palbociclib for the treatment of patients with locally advanced or metastatic HR+/HER2- breast cancer following progression on or after CDK4/6 and aromatase inhibitor therapy.

Description:

This is a Phase 3, open-label, randomized clinical trial evaluating the efficacy and safety of gedatolisib plus fulvestrant with or without palbociclib for the treatment of patients with advanced (inoperable) or metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) breast cancer following progression on or after CDK4/6 and aromatase inhibitor therapy. Gedatolisib is an intravenously administered pan-PI3K/mTOR inhibitor. Palbociclib is a CDK4/6 inhibitor. Fulvestrant is a selective estrogen receptor degrader (SERD). Subjects will be assessed for PIK3CA status and then randomized to treatment arms according to their confirmed PIK3CA mutation status.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 701
• Est. completion date: September 30, 2026
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of metastatic or locally advanced breast cancer Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with an LHRH agonist. Patients are to have commenced concomitant treatment with LHRH agonist prior to or on Cycle 1, Day 1 and must be willing to continue on it for the duration of the study.

2. Negative pregnancy test for women of childbearing potential. Female subjects of childbearing potential must use an effective and/or acceptable contraceptive method from screening until 1 year after the last dose of study treatment

3. Confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive, as per American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines (2020), based on most recent tumor biopsy utilizing an assay consistent with local standards

4. Documented HER2 immunohistochemistry (IHC) negative as per ASCO-CAP 2018 guidance

5. Adequate archival or fresh tumor tissue for the analysis of PIK3CA mutational status

6. Subject must have documentation of radiological disease progression on or after the last prior treatment and also have radiologically evaluable disease (measurable and/or non-measurable) according to RECIST v1.1, per local assessment. Subjects with bone only disease must have lytic or mixed lytic/blastic lesions that can be accurately assessed; bone only blastic lesions with no soft tissue component is not allowed.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

8. Life expectancy of at least 3 months

9. Progressed during or after CDK4/6 inhibitor combination treatment with non-steroidal aromatase inhibitor (AI)

10. Adequate bone marrow, hepatic, renal and coagulation function

Exclusion Criteria:

1. History of malignancies other than adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for =3 years

2. Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor, a protein kinase B (Akt) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor

3. Prior treatment with chemotherapy and antibody drug conjugates for advanced disease is not permitted (prior adjuvant or neoadjuvant chemotherapy is permitted)

4. More than 2 lines of prior endocrine therapy treatment

5. Bone only disease that is only blastic with no soft tissue component

6. Subjects with type 1 diabetes or uncontrolled type 2 diabetes

7. Known and untreated, or active, brain or leptomeningeal metastases

a. Subjects with previously treated central nervous system (CNS) metastases may be enrolled in the study if they meet the following criteria: do not require supportive therapy with steroids; do not have seizures and do not exhibit uncontrolled neurological symptoms; stable disease confirmed by radiographic assessment within at least 4 weeks prior to enrollment

8. Patients with advanced, symptomatic, visceral spread that are at risk of life-threatening complication in the short-term

9. History of clinically significant cardiovascular abnormalities such as: Congestive heart failure (New York Heart Association (NYHA) classification = II within 6 months of study entry

1. Myocardial infarction within 12 months of study entry

2. History of any uncontrolled (or untreated) clinically significant cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle branch block, high grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block), supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months

3. Uncontrolled hypertension defined by systolic blood pressure (SBP) =160 mmHg and/or diastolic blood pressure (DBP) =100 mmHg, with or without antihypertensive medication (initiation or adjustment of antihypertensive medication[s] is allowed prior to screening)

4. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:

• i. Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, or history of clinically significant/symptomatic bradycardia

• ii. On screening, inability to determine the corrected QT interval using Fridericia's formula (QTcF) on the ECG (i.e., unreadable or not interpretable) or QTcF >480 msec (determined by mean of triplicate ECGs at screening)

10. Known hypersensitivity to the study drugs or their components

11. Pregnant or breast-feeding women

12. Concurrent participation in another interventional clinical trial

1. Subjects must agree not to participate in another clinical trial (other than observational) at any time during participation in VIKTORIA-1.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Gedatolisib
Gedatolisib 180 mg IV given weekly for 3 weeks (Days 1, 8, 15) followed by 1 week off
• Palbociclib
Palbociclib 125 mg PO given daily for 3 weeks (21 days), followed by 1 week off
• Fulvestrant
Fulvestrant 500 mg IM (2 × 5 mL injections) given every 2 weeks during Cycle 1 (Days 1 and 15), then every 4 weeks beginning with Cycle 2 Day 1
• Alpelisib
Alpelisib 300 mg PO (2 × 150 mg tablets) given daily for 4 weeks (28 days)

Locations

Country	Name	City	State
Argentina	Alexander Fleming Institute	Buenos Aires
Argentina	Buenos Aires British Hospital	Buenos Aires
Argentina	CENIT Foundation	Buenos Aires
Argentina	Center for Medical Education and Clinical Research (CEMIC)	Buenos Aires
Argentina	Fleischer Medical Center	Buenos Aires
Argentina	Medical Center Austral	Buenos Aires
Argentina	Pergamino Clinic	Buenos Aires
Argentina	Cordoba Oncology Institute (IONC)	Córdoba
Argentina	Center of Nuclear and Molecular Medicine of Entre Rios (CEMENER)	Paraná
Argentina	CEDIT Diagnostic and treatment center	Salta
Argentina	CER San Juan	San Juan
Argentina	Rosario's Oncology Institute and Medical Specialities (IOR)	Santa Fe
Argentina	9 of July Sanatorium	Tucumán
Australia	Adelaide Oncology & Haematology	Adelaide
Australia	St Vincent's Hospital (Melbourne) Ltd	Fitzroy
Australia	Peninsula & South Eastern Hematology and Oncology Group (PSEHOG)	Frankston
Australia	Hollywood Private Hospital, Breast Cancer Research Centre	Nedlands
Australia	Mater Hospital Brisbane, Mater Cancer Care Centre	South Brisbane
Australia	Icon Cancer Centre- Southport	Southport
Australia	Sydney Adventist Hospital	Wahroonga
Australia	The Queen Elizabeth Hospital	Woodville
Austria	University Hospital Graz, Department of Gynecology and Obstetrics	Graz
Austria	University Hospital Innsbruck - Tyrolean Hospital, Department of Gynaecology and Obstetrics	Innsbruck
Austria	Order Hospital Linz Ltd. - Hospital of Sisters of Mercy, Department of Internal Medicine I	Linz
Austria	Salzburg Regional Hospital, Department of Internal Medicine III	Salzburg
Austria	University Hospital St. Poelten, Department of Internal Medicine I	St. Poelten
Austria	Hospital Hietzing, Department of Gynecology	Vienna
Austria	Medical University Vienna, Department of Gynecology and Obstetrics	Vienna
Belgium	Saint Luc University Hospital	Brussels
Belgium	Charleroi Grand Hospital (GHDC)	Charleroi
Belgium	University Hospital Antwerp (UZA)	Edegem
Belgium	AZ Groeninge	Kortrijk
Belgium	University Hospitals Leuven, Campus Gasthuisberg	Leuven
Belgium	Citadelle Regional Hospital Center	Liège
Belgium	VITAZ	Sint-Niklaas
Belgium	Centre Hospitalier Peltzer-la-Tourelle	Verviers
Belgium	UCL Mont-Godinne University Hospitals	Yvoir
Brazil	Oncology Treatment Center	Belém	Pará
Brazil	Pronutrir	Fortaleza
Brazil	ONCOSITE - Clinical Research Center in Oncology	Ijuí
Brazil	Juiz de Fora Eurolatino Research Center	Minas Gerais
Brazil	Bahia Oncology Center	Salvador de Bahia
Brazil	D'OR Institute	São Paulo
Brazil	Hospital A.C.Camargo	São Paulo
Bulgaria	Multiprofile Hospital for Active Treatment - Uni Hospital, Panagyurishte	Panagyurishte
Bulgaria	MHAT for Women's Health "Nadezhda"	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment "Serdika", Sofia	Sofia
Bulgaria	Specialized Hospital for Active Treatment in Oncology, Clinic of Medicial Oncology (Chemotherapy)	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment "Sveta Marina"	Varna
Canada	CIUSSS du Saguenay Lac St-Jean	Chicoutimi	Quebec
Canada	Hospital Notre-Dame	Montréal	Quebec
Canada	Maisonneuve-Rosemont Hospital	Montréal	Quebec
Canada	BC Cancer - Vancouver, Medical Oncology	Vancouver	British Columbia
Czechia	University Hospital Olomouc, Clinic of Oncology	Olomouc
Czechia	Thomayer University Hospital, Clinic of Oncology	Prague
Czechia	University Hospital Bulovka, Institute of Radiation Oncology	Prague
Czechia	University Hospital Motol, Clinic of Oncology	Prague
France	Bergonie Institute	Bordeaux
France	Francois Baclesse Center	Caen
France	La Roche-sur-Yon Hospital	La Roche-sur-Yon
France	CHU La Timone - La Timone Children's Hospital	Marseille
France	University Hospital Center of Poitiers	Poitiers
France	Saint Anne Clinic	Strasbourg
France	Gustave Roussy	Villejuif
Germany	Hospital Bayreuth	Bayreuth
Germany	Vivantes Hospital Am Urban	Berlin
Germany	Private Practice with Focus on Oncology	Luebeck
Germany	University Hospital Johannes Gutenberg - University of Mainz	Mainz
Germany	Hospital Suedstadt Rostock	Mecklenburg
Germany	University Hospital Muenster	Münster
Germany	Caritas Klinikum	Saarbrücken
Germany	Helios Clinic Wuppertal	Wuppertal
Greece	Alexandra General Hospital	Athens
Greece	University General Hospital of Ioannina	Ioánnina
Greece	IASO Thessaly SA	Larissa
Greece	EUROMEDICA General Clinic of Thessaloniki	Thessaloníki
Greece	Theageneio Anticancer Hospital of Thessaloniki	Thessaloníki
Hungary	University of Debrecen Clinical Center, Institute of Oncology	Debrecen
Hungary	Bacs-Kiskun County Hospital, Center for Oncoradiology	Kecskemét
Hungary	Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of Oncology	Nyíregyháza
India	HCG Cancer Centre	Bangalore
India	Postgraduate Institute of Medical Education and Research (PGIMER)	Chandigarh
India	Tata Medical Center	Kolkata
India	Tata Memorial Hospital	Navi Mumbai
India	Christian Medical College, Department of Medical Oncology	Vellore
Italy	European Institute of Oncology (IEO), IRCCS	Milan
Italy	University Polyclinic Hospital of Modena	Modena
Italy	Local Healthcare Company of Monza (ASST Monza)	Monza
Italy	University Hospital of Parma	Parma
Italy	New Hospital of Prato (NOP)	Prato
Italy	University Hospital Campus Bio-Medico	Rome
Italy	University Polyclinic Foundation "Agostino Gemelli" - IRCCS	Rome
Italy	Santa Maria della Misericordia University Hospital of Udine	Udine
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Soeul
Korea, Republic of	Korea University Anam Hospital	Soeul
Korea, Republic of	Samsung Medical Center	Soeul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Soeul
Korea, Republic of	Ulsan University Hospital	Ulsan
Mexico	Clinical Research Center Chapultepec Mexico City	Mexico City
Mexico	CRYPTEX	Mexico City
Mexico	ProcliniQ Clinical Research	Mexico City
Mexico	Filios High Medicine	Monterrey
Mexico	Administrative Society of Health Services, SC	Morelia
Mexico	Avix Clinical Research	Nuevo León
Mexico	Zambrano Hellion Medical Center	Nuevo León
Mexico	Inbiomedyc	Querétaro
Mexico	ONCOR Life Medical Center	Saltillo
Poland	Prof. Franciszek Lukaszczyk Oncology Center in Bydgoszcz, Chemotherapy Outpatient Clinic	Bydgoszcz
Poland	Medical Clinic "Komed"	Konin
Poland	Maria Sklodowska-Curie Institute of Oncology, Branch in Krakow	Kraków
Poland	Polish Mother's Memorial Hospital-Research Institute	Lódz
Poland	Independent Public Healthcare Facility Prof. Tadeusz Koszarowski Opole Oncology Center in Opole, Clinical Oncology Department and Day Hospitalization Unit	Opole
Poland	St. John Paul 2nd Mazovian Provincial Hospital in Siedlce Limited Liability Company, Siedlce Oncology Centre	Siedlce
Poland	West Pomeranian Oncology Center	Szczecin
Poland	LUX MED Oncology LLC, Szamocka Hospital, Department of Clinical Oncology/Chemotherapy	Warsaw
Poland	Maria Sklodowska-Curie - National Research Institute of Oncology	Warsaw
Poland	Provincial Specialist Hospital in Wroclaw, Department of Chemotherapy	Wroclaw
Romania	S.C. Oncopremium-Team SRL	Baia Mare
Romania	Prof. Dr. Alexandru Trestioreanu Institute of Oncology	Bucharest
Romania	Prof. Dr. Ion Chiricuta Institute of Oncology	Cluj-Napoca
Romania	Onco Clinic Consult S.A.	Craiova
Romania	Oncology Center "Sf. Nectarie"	Craiova
Romania	S.C. Topmed Medical Center SRL	Târgu-Mures
Singapore	Curie Oncology	Singapore
Singapore	ICON SOC Farrer Park Medical Clinic	Singapore
Singapore	OncoCare Cancer Centre	Singapore
Singapore	Raffles Hospital	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
Spain	Infanta Cristina Hospital	Badajoz
Spain	Catalan Institute of Oncology, Hospital Duran i Reynals	Barcelona
Spain	Caceres Hospital Complex - San Pedro de Alcantara General Hospital	Cáceres
Spain	Hospital Ruber Internacional	Madrid
Spain	University Hospital Foundation Jimenez Diaz	Madrid
Spain	University Clinical Hospital Virgen de la Arrixaca, Department of Oncology	Murcia
Spain	University Hospital Complex of Santiago (CHUS), Department of Oncology	Santiago De Compostela
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Taipei Medical University - Shuang Ho Hospital	New Taipei City
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United Kingdom	Royal United Hospital, Department of Oncology/Hematology	Bath
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Guy's Hospital	London
United Kingdom	Royal Marsden Hospital - London, Department of Medical Oncology	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Nottingham City Hospital	Nottingham
United States	New York Oncology Hematology, P.C. - Albany	Albany	New York
United States	Pacific Cancer Medical Center Inc	Anaheim	California
United States	Illinois Cancer Specialists - Arlington Heights	Arlington Heights	Illinois
United States	Texas Oncology - Austin	Austin	Texas
United States	American Oncology Partners of Maryland, PA	Bethesda	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Consultants In Medical Oncology and Hematology, P.C.	Broomall	Pennsylvania
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	The James Cancer Hospital and Solove Research Institute	Columbus	Ohio
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology P.A. - Dallas	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	William Beaumont Army Medical Center	El Paso	Texas
United States	Fort Belvoir Community Hospital	Fort Belvoir	Virginia
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Arizona Oncology (US Oncology/McKesson) - Goodyear	Goodyear	Arizona
United States	Cone Health Cancer Center at Alamance Regional, Hematology/Oncology	Greensboro	North Carolina
United States	Kaiser Permanente South Bay Medical Center	Harbor City	California
United States	South Broward Hospital District d/b/a Memorial Healthcare System	Hollywood	Florida
United States	Alliance Cancer Specialists PC	Horsham	Pennsylvania
United States	Brooke Army Medical Center	Houston	Texas
United States	Oncology Consultants	Houston	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Cancer Specialists of North Florida - Jacksonville	Jacksonville	Florida
United States	Queens Hospital Cancer Center	Jamaica	New York
United States	St. Bernards Medical Center	Jonesboro	Arkansas
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	Nebraska Hematology - Oncology, P.C.	Lincoln	Nebraska
United States	CARTI Cancer Center	Little Rock	Arkansas
United States	Cancer and Blood Specialty Clinic	Los Alamitos	California
United States	Southeast Regional Cancer Center	Lumberton	North Carolina
United States	Texas Oncology - McKinney	McKinney	Texas
United States	Bon Secours St. Francis Medical Oncology Center	Midlothian	Virginia
United States	Pacific Cancer Care	Monterey	California
United States	Yale Cancer Center - New Haven	New Haven	Connecticut
United States	Coleman, Pasmantier & Decter, MDs	New York	New York
United States	Weill Cornell Medicine/New York-Presbyterian Hospital	New York	New York
United States	Virginia Oncology Associates - Newport News	Newport News	Virginia
United States	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Oncology Hematology West PC dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of California, Irvine Medical Center	Orange	California
United States	Ventura County Hematology Oncology Specialists	Oxnard	California
United States	Mercy Health - Paducah	Paducah	Kentucky
United States	Redlands Hematology Oncology	Redlands	California
United States	VCU Massey Cancer Center	Richmond	Virginia
United States	Oncology & Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care - Roanoke	Roanoke	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	Maryland Oncology Hematology, P.A. - Rockville	Rockville	Maryland
United States	Oregon Oncology Specialists	Salem	Oregon
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	UCLA Hematology/Oncology-Santa Monica	Santa Monica	California
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Sanford Gynecologic Oncology Clinic	Sioux Falls	South Dakota
United States	Texas Oncology - Gulf Coast	Sugar Land	Texas
United States	Hematology/Oncology Associates of Central New York	Syracuse	New York
United States	Northwest Medical Specialties, PLLC - Tacoma	Tacoma	Washington
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	John D. Archbold Memorial Hospital	Thomasville	Georgia
United States	Northwest Cancer Specialists, PC - Tigard	Tigard	Oregon
United States	Torrance Memorial Physician Network - Cancer Care	Torrance	California
United States	Texas Oncology - Tyler	Tyler	Texas
United States	Kaiser Permanente Medical Center - Vallejo	Vallejo	California
United States	White Plains Hospital	White Plains	New York
United States	PIH Health Hospital Whittier	Whittier	California
United States	Bond & Steele Clinic, P.A. d/b/a Bond Clinic, P.A.	Winter Haven	Florida
United States	Cancer Care Associates of York	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Celcuity, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Greece,  Hungary,  India,  Italy,  Korea, Republic of,  Mexico,  Poland,  Romania,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer	PFS is defined as the time from randomization to death or the first documented progression, whichever occurs first, confirmed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, as determined based on blinded independent central review (BICR)	Approximately 48 months
Secondary	Overall Survival (OS) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer	OS is defined as the length of time from randomization until the date of death from any cause method, where PFS is defined as the time from randomization to death or the first documented progression, whichever occurs first, confirmed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, as determined based on blinded independent central review (BICR)	From date of randomization to the date of death due to any cause, up to approximately 48 months
Secondary	Overall Response Rate (ORR) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer	Percentage of subjects who achieved an objective response according to RECIST v1.1 criteria (complete response [CR] or partial response [PR]) as assessed by BICR)	Up to approximately 48 months
Secondary	Duration of Response (DOR) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer	Time from the assessment of initial response (PR or better) to death or first documented disease progression as assessed by BICR, whichever occurs first	Up to approximately 48 months
Secondary	Time to Response (TTR) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer	Time form randomization to the first assessment of PR or better as assessed by BICR, whichever comes first	Up to approximately 48 months
Secondary	Clinical Benefit Rate (CBR) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer	Percentage of subjects with CR, PR, or stable disease (SD) >24 weeks as assessed by BICR	Up to approximately 48 months
Secondary	Quality of Life (QOL)Functional Assessment of Cancer Therapy - Breast Trial Outcome Index (FACT-B TOI) Questions in Patients with PIK3CA WT and PIK3CA MT Breast Cancer	The FACT-B TOI is an abbreviated (24-item) version of the full FACT-B which focuses only on the patient's Physical Well-being (PWB), Functional Well-being (FWB), and Breast Cancer Subscale (BCS) components using a 5-level scale, (Not at all, A little bit, Some-what, Quite a bit, Very much).	From baseline to 30 Day Safety Follow-up
Secondary	Quality of Life (QOL) NCCN-FACT Breast Symptom Index -16 (NFBSI-16) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer	NCCN-FACT is derived from the FACT-B and only 4 additional items will be administered to enable optional scoring of the NFBSI subscales and total score using a 5-level scale (Not at all, A little bit, Some-what, Quite a bit, Very much).	From baseline to 30 Day Safety Follow-up
Secondary	Patient-Reported Outcomes in Patients with PIK3CA WT and PIK3CA MT Breast Cancer	Patient-Reported Outcomes Measurement Information System (PROMIS®) Short Form v2.0 - Physical Function 8c using a 5-level scale (Without any difficulty, With a little difficulty, With some difficulty, With much difficulty, Unable to do)	From baseline to 30 Day Safety Follow-up
Secondary	EuroQol 5 in Patients with PIK3CA WT and PIK3CA MT Breast Cancer	EuroQol 5 Dimension 5 Level (EQ-5D-5L) - This is a 5 question, self-administered visual analog scale (VAS) where patients use 0 (worst health) to 100 (best health) to indicate how they view their health.	From baseline to 30 Day Safety Follow-up
Secondary	Adverse Events	Safety and tolerability will be evaluated by review of type, incidence, severity (as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0), seriousness, and relationship to study medications of adverse events (AEs) and any laboratory abnormalities	Up to approximately 48 months