Clinical trial NCT06757634: Phase 3 Study of Gedatolisib as First-Line Treatment for Patients With HR-Positive, HER2-Negative Advanced Breast Cancer (VIKTORIA-2)
Official title: VIKTORIA-2: A Randomized, Open-Label, Phase 3 Study of Fulvestrant and CDK4/6 Inhibitors With or Without Gedatolisib as First-Line Treatment in Patients With HR-Positive and HER2-Negative Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Breast Cancer, Advanced or Metastatic
Gedatolisib
HR Positive
ER Positive
HER2 Negative
PIK3CA MT
PI3K
Lead sponsor: Celcuity Inc
Sponsor class: INDUSTRY
First posted: 2025-01-03
Enrollment: 674
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, open-label, randomized, clinical trial evaluating the efficacy and safety of gedatolisib plus fulvestrant and CDK4/6 Inhibitors for the treatment of patients with locally advanced or metastatic HR+/HER2- advanced breast cancer.

Detailed description: This is a Phase 3, open-label, randomized clinical trial evaluating the efficacy and safety of gedatolisib plus fulvestrant combined with a CDK4/6 inhibitor (Investigator's choice of palbociclib or ribociclib) for the treatment of patients with advanced (inoperable) or metastatic hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer whose disease has progressed during or within 12 months of adjuvant treatment with endocrine therapy (either an AI or tamoxifen), and who have not received prior systemic therapy for ABC. Gedatolisib is an intravenously administered pan-PI3K/mTOR inhibitor. Palbociclib is a CDK4/6 inhibitor. Fulvestrant is a selective estrogen receptor degrader (SERD). Following completion of the safety run-in phase to determine the gedatolisib dose with ribociclib, subjects will be assigned to 1 of 2 cohorts based on their PIK3CA status and then randomized to either the investigational treatment arm (gedatolisib with fulvestrant and ribociclib or palbociclib) or standard-of-care control arm (fulvestrant and ribociclib or palbociclib).

Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of metastatic or locally advanced HR+/HER2- breast cancer
2. 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 for the duration of the study.
3. Negative pregnancy test for females of childbearing potential. Female subjects who are not surgically sterile must use a medically effective contraceptive method from screening until 2 years after the last dose of study treatment.
4. Progression of disease during or within 12 months of completing (neo)adjuvant ET.
5. Adequate archival, fresh tumor tissue, or liquid biopsy for the analysis of PIK3CA mutational status.
6. Permitted prior therapies:

   1. (neo)adjuvant fulvestrant or any selective ER degrader only if the treatment duration \< 6 months
   2. (neo)adjuvant chemotherapy
   3. (neo)adjuvant CDK4/6 inhibitor, unless PD was on or within 6 months of discontinuation of CDK4/6i
7. Subject has radiologically measurable disease according to RECIST v1.1, per local assessment. Patients with evaluable bone-only disease are not eligible. Patients with bone-only disease that has lytic or mixed lytic/blastic lesions and at least one measurable soft tissue component per RECIST v1.1 may be eligible.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
9. Life expectancy of at least \>6 months.
10. Adequate bone marrow, hepatic, renal and coagulation function.

Exclusion Criteria:

1. Concurrent malignancies other than adequately treated non-melanoma skin cancer. Previous malignancies in remission but curatively treated with no evidence of disease progression and judged by local Investigator to be at low risk of impacting health or survival while on study.
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 systemic anticancer therapy for ABC
4. Subjects with type 1 diabetes
5. Known and untreated, or active, brain or leptomeningeal metastases
6. History of clinically significant cardiovascular abnormalities
7. History of drug-induced symptomatic interstitial lung disease (pneumonitis) or hepatitis

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From date of randomization to the date of death due to any cause, up to approximately 48 months
Secondary outcomes:
measure: Overall Survival (OS) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer
timeFrame: From date of randomization to the date of death due to any cause, up to approximately 48 months
measure: Overall Response Rate (ORR) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer
timeFrame: Up to approximately 48 months
measure: Overall Response Rate (ORR) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer
timeFrame: Up to approximately 48 months
measure: Duration of Response (DOR) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer
timeFrame: Up to approximately 48 months
measure: Time to Response (TTR) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer
timeFrame: Time from randomization to the first assessment of PR or better as assessed by BICR
measure: Clinical Benefit Rate (CBR) in Patients with PIK3CA ND and PIK3CA MT Breast Cancer
timeFrame: Up to approximately 48 months
measure: Quality of Life (QOL) Functional Assessment of Cancer Therapy - Breast Trial Outcome Index (FACT-B TOI)
timeFrame: From baseline to 30 Day Safety Follow-up
measure: Adverse Events
timeFrame: Up to approximately 48 months
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology Oncology Ventura
state: California
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Paducah
country: United States
facility: Mercy Health-Paducah Cancer Center
state: Kentucky
city: Bethesda
country: United States
facility: American Oncology Partners, P.A.
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine in Saint Louis
state: Missouri
city: Billings
country: United States
facility: SCL Health - Cancer Centers of Montana
state: Montana
city: New York
country: United States
facility: Weill Cornell Medical College - NewYork-Presbyterian Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center (URMC) - James P. Wilmot Cancer Center - Pluta Cancer Center (PCC)
state: New York
city: Westbury
country: United States
facility: Clinical Research Alliance, Inc.
state: New York
city: Columbus
country: United States
facility: Stefanie Spielman Comprehensive Breast Center at Olentangy River Road
state: Ohio
city: Philadelphia
country: United States
facility: Rittenhouse Hematology/Oncology
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Health
state: South Dakota
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Mays Cancer Center
state: Texas
city: Midlothian
country: United States
facility: Bon Secours St. Francis Medical Oncology Center
state: Virginia
city: Buenos Aires
country: Argentina
facility: Centro de Oncologia e Investigacion Buenos Aires COIBA
city: Buenos Aires
country: Argentina
facility: Pergamino Clinic
city: Buenos Aires
country: Argentina
facility: CENIT Foundation
city: Buenos Aires
country: Argentina
facility: Fleischer Medical Center (Centro Medico Fleischer)
city: Buenos Aires
country: Argentina
facility: Fundacion Respirar
city: Buenos Aires
country: Argentina
facility: Centro Oncológico Korben
city: Buenos Aires
country: Argentina
facility: Alexander Fleming Institute
city: Buenos Aires
country: Argentina
facility: Center for Medical Education and Clinical Research (CEMIC)
city: Córdoba
country: Argentina
facility: Cordoba Oncology Institute (IONC)
city: La Plata
country: Argentina
facility: Centro Oncologico de Excelencia
city: La Rioja
country: Argentina
facility: Fundación CORI
city: Paraná
country: Argentina
facility: Center of Nuclear and Molecular Medicine of Entre Rios (CEMENER)
city: Rosario
country: Argentina
facility: Rosario's Oncology Institute and Medical Specialities (IOR)
city: Adelaide
country: Australia
facility: GenesisCare - St Andrews
city: Nedlands
country: Australia
facility: Breast Cancer Research Centre
city: Southport
country: Australia
facility: Icon Cancer Centre Southport
city: Wahroonga
country: Australia
facility: Sydney Adventist Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Charleroi
country: Belgium
facility: Grand Hopital De Charleroi
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent - Medische Oncologie
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis - Campus Virga Jesse - Medische Oncologie
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Belo Horizonte
country: Brazil
facility: Oncocentro Belo Horizonte
city: Belém
country: Brazil
facility: CTO Centro de Tratamento Oncológico
city: Fortaleza
country: Brazil
facility: Centro Regional Integrado de Oncologia - CRIO
city: Fortaleza
country: Brazil
facility: Pronutrir Oncologia e Nutrição
city: Ijuí
country: Brazil
facility: ONCOSITE - Centro de Pesquisa Clinica em Oncologia LTDA
city: Itajaí
country: Brazil
facility: Catarina Pesquisa Clinica
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUCRS
city: Ribeirão Preto
country: Brazil
facility: Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP
city: Salvador
country: Brazil
facility: Bahia Oncology Center
city: São Paulo
country: Brazil
facility: Hospital A.C.Camargo
city: São Paulo
country: Brazil
facility: Instituto D'or de Pesquisa e Ensino - ONCO STAR
city: Burgas
country: Bulgaria
facility: Complex Oncology Center - Burgas
city: Panagyurishte
country: Bulgaria
facility: Multi-profile Hospital For Active Treatment-Uni Hospital Ltd.
city: Ruse
country: Bulgaria
facility: Complex Oncological Centre Ruse
city: Sofia
country: Bulgaria
facility: MHAT Nadezhda - Medical Oncology Clinic
city: Sofia
country: Bulgaria
facility: MHAT "Serdika" EOOD, Base 2 - Second Department of Medical Oncology
city: Sofia
country: Bulgaria
facility: USHAT of Oncology
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav - Oddeleni klinickych hodnoceni
city: Hořovice
country: Czechia
facility: Multiscan s.r.o. - Ambulance klinicke onkologie se stacionarem
city: Hradec Králové
country: Czechia
facility: FN Hradec Kralove - Klinika onkologie a radioterap
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc - Onkologicka klinika
city: Praha 10
country: Czechia
facility: FN Kralovske Vinohrady - Radioterapeuticka a onkologicka klinika
city: Praha 4
country: Czechia
facility: Fakultni Thomayerova Nemocnice - Onkologicka klinika
city: Praha 5
country: Czechia
facility: Fakultni Nemocnice v Motole
city: Amiens
country: France
facility: Centre Hospitalier Universitaire D'Amiens (Hopital Sud) - Oncologie Medicale - Cancerolo
city: Caen
country: France
facility: Centre Georges François Baclesse
city: Dijon
country: France
facility: Centre Georges Francois Leclerc - service d'oncologie médicale
city: Le Mans Cedex 2
country: France
facility: Clinique Victor Hugo / Centre Jean Bernard
city: Marseille
country: France
facility: APHM Hopital Timone
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers - Médico-Chirurgical De Cardiol
city: St Herblain
country: France
facility: Centre de Lutte Contre le Cancer (CLCC) - Institut de Cancerologie de l'Ouest (ICO) - Rene Gauducheau - Oncology
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf - Gynecology
city: Mainz
country: Germany
facility: Universitätsmedizin Johannes Gutenberg
city: Saarbrücken
country: Germany
facility: CaritasKlinikum Saarbrücken St. Theresia
city: Wuppertal
country: Germany
facility: Helios Klinikum Wuppertal
city: Athens
country: Greece
facility: Areteio Hospital
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion
city: Larissa
country: Greece
facility: Iaso Thessalia General Clinic Private Obstetrics S.A.
city: Larissa
country: Greece
facility: General University Hospital Of Larissa
city: Piraeus
country: Greece
facility: Metropolitan Hospital
city: Thessaloníki
country: Greece
facility: Athens Medical Center S.A.
city: Thessaloníki
country: Greece
facility: Theageneio Cancer Hospital
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ Nagyerdei Campus - Onkológiai Klinika
city: Gyula
country: Hungary
facility: Bekes Varmegyei Kozponti Korhaz Pandy Kalman Tagkorhaza
city: Győr
country: Hungary
facility: Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktatokorhaz
city: Kecskemét
country: Hungary
facility: Bacs-Kiskun Varmegyei Oktatakorhaz
city: Pécs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Szekszárd
country: Hungary
facility: Tolna Varmegyei Balassa Janos Korhaz
city: Genova
country: Italy
facility: Ospedale San Martino IRCSS - Oncologia Medica 1
city: Meldola
country: Italy
facility: Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.R.L
city: Milano
country: Italy
facility: IEO - Istituto Europeo di Oncologia, IRCCS
city: Milano
country: Italy
facility: Istituto Clinico Humanitas
city: Modena
country: Italy
facility: AOU di Modena, Policlinico di Modena - Attività Integrata di Oncologia ed Ematologia
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori - Fondazione Pascale, IRCCS
city: Parma
country: Italy
facility: Ospedale Maggiore, AOU Parma
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo, Università degli studi di Pavia
city: Roma
country: Italy
facility: Fondazione PU Campus Biomedico
city: Roma
country: Italy
facility: Umberto I Policlinico di Roma, Università La Sapienza
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria di Terni
city: Terni
country: Italy
facility: Ospedale "Santa Maria delle Croci" di Ravenna - Oncologia
city: Verona
country: Italy
facility: Borgo Trento, Ospedale Civile Maggiore, AOU Integrata Verona
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital - Gastroenterological Surgery
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - Oncology
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center - Hematology & Oncology
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Suwon-Si
country: Korea, Republic of
facility: Ajou University Hospital - Hematology/Oncology
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Kota Bahru
country: Malaysia
facility: Hospital Universiti Sains Malaysia
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur - Surgery
city: Kuala Lumpur
country: Malaysia
facility: Pantai Hospital Kuala Lumpur
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
city: Putrajaya
country: Malaysia
facility: Institut Kanser Negara
city: Aguascalientes
country: Mexico
facility: San Peregrino Unidad de Investigacion
city: Ciudad de Mexico
country: Mexico
facility: Clinical Research Center Chapultepec Mexico City
city: Ciudad de Mexico
country: Mexico
facility: Centro de Atencion Oncologica Viva
city: Guadalajara
country: Mexico
facility: Office of Emanuel de la Mora Jimenez, MD/equiv
city: Monterrey
country: Mexico
facility: Avix Clinical Research
city: Monterrey
country: Mexico
facility: Filios High Medicine
city: Morelia
country: Mexico
facility: Administrative Society of Health Services, SC
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. prof. F. Lukaszczyka - Ambulatorium Chemioterapii
city: Konin
country: Poland
facility: Przychodnia Lekarska KOMED
city: Kraków
country: Poland
facility: Pratia MCM Kraków
city: Lodz
country: Poland
facility: Instytut Medyczny Santa Familia
city: Opole
country: Poland
facility: SP ZOZ Opolskie Centrum Onkologii - Oddzial Onkologii Klinicznej z Odcinkiem Dziennym
city: Szczecin
country: Poland
facility: Zachodniopomorskie Centrum Onkologii - Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych
city: Warszawa
country: Poland
facility: LUX MED Onkologia Sp. z o.o., Szpital Szamocka - Oddzial Onkologii Klinicznej/Chemioterapii
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii SkÅ'odowskiej-Curie â€" PaÅ"stwowy Instytut Badawczy - Klinika Nowotworow Piersi i Chirurg
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitário de Coimbra
city: Lisboa
country: Portugal
facility: Instituto Portugues de Oncologia de Lisboa Francisco Gentil - Oncologia Medica
city: Lisboa
country: Portugal
facility: Hospital da Luz de Lisboa - Learning Health
city: Lisboa
country: Portugal
facility: H. de Santa Maria. Centro Hospitalar Lisboa Norte - Oncologia
city: Lisboa
country: Portugal
facility: Hospital CUF Descobertas
city: Porto
country: Portugal
facility: ULS de Santo Antonio E.P.E.
city: Baia Mare
country: Romania
facility: Centrul de Oncologie Sf Nectarie - Medical Oncology
city: Baia Mare
country: Romania
facility: Oncopremium Team - Medical Oncology
city: Bucuresti
country: Romania
facility: Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic Prof Dr Alexandru Trestioreanu Bucuresti
city: Craiova
country: Romania
facility: Onco Clinic Consult
city: Floresti
country: Romania
facility: Radiotherapy Center Cluj
city: Iaşi
country: Romania
facility: Centrul de Oncologie Euroclinic
city: Iaşi
country: Romania
facility: Institutul Regional de Oncologie Iasi - Medical Oncology
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
city: Badajoz
country: Spain
facility: Hospital Universitario de Badajoz
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Hospital Clinic De Barcelona
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: El Palmar
country: Spain
facility: Hospital Clínico Universitario Virgen De La Arrixaca
city: L'Hospitalet De Llobregat
country: Spain
facility: Institut Catala D'oncologia
city: Lleida
country: Spain
facility: H.U Arnau De Vilanova Lleida
city: Madrid
country: Spain
facility: Hospital Beata Maria Ana
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal - Oncología Médica
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario De Santiago
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncologia
city: Changhua City
country: Taiwan
facility: Changhua Christian Medical Foundation - Changhua Christian Hospital - Neurology
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University - Chung-Ho Memorial Hospital - Breast Surgery
city: Taichung
country: Taiwan
facility: China Medical University Hospital - Breast Surgery
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital - Gynecology/Obstetrics
city: Taipei City
country: Taiwan
facility: Taipei Medical University - Shuang Ho Hospital Ministry of Health and Welfare - Nephrology
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital - Hematology
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital - Oncology
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital [Medical Oncology]
city: Bangkok
country: Thailand
facility: Rajavithi Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital - Medical Oncology
city: Hat Yai
country: Thailand
facility: Prince of Songkla University - Internal Medicine
city: Samut Sakhon
country: Thailand
facility: Banphaeo General Hospital
city: Adana
country: Turkey
facility: Medical Park Seyhan Hastanesi
city: Ankara
country: Turkey
facility: Gulhane Egitim Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty - Hematology
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty - Oncology
city: Diyarbakir
country: Turkey
facility: Dicle Universitesi Hastanesi
city: Edirne
country: Turkey
facility: Trakya Univ Hastanesi Ic Hastal
city: Istanbul
country: Turkey
facility: Medipol Mega Hospital - Medical Oncology
city: Istanbul
country: Turkey
facility: Medical Park Florya Hastanesi
city: Istanbul
country: Turkey
facility: Goztepe SuleymanYalcin Sehir Hast
city: İzmir
country: Turkey
facility: Izmir Medical Park Hospital - Medical Oncology
city: Izmit
country: Turkey
facility: Kocaeli Uni Uyg ve Ars Hst
city: Konya
country: Turkey
facility: Necmettin Erbakan University Meram Medical Faculty - Oncology
city: Mersin
country: Turkey
facility: VM Medical Park Mersin Hastanesi
Study officials:
References: