Clinical trial NCT06790693: A Study Evaluating the Efficacy and Safety of Inavolisib Plus CDK4/6 Inhibitor and Letrozole vs Placebo + CDK4/6i and Letrozole in Participants With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer
Official title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib Plus a CDK4/6 Inhibitor and Letrozole Versus Placebo Plus a CDK4/6 Inhibitor and Letrozole in Patients With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2025-01-24
Enrollment: 450
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 study will evaluate the efficacy and safety of the combination of inavolisib plus a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) and letrozole versus placebo plus a CDK4/6i and letrozole in the first-line setting in participants with endocrine-sensitive PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer (ABC).


Eligibility criteria: Inclusion Criteria:

* Women or men with histologically or cytologically confirmed carcinoma of the breast
* Documented ER-positive and/or progesterone receptor-positive tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
* Documented HER2-negative tumor according to ASCO/CAP guidelines
* De-novo HR+ , HER2- ABC, or, alternatively, relapsed HR+ , HER2- ABC after at least 2 years of standard neoadjuvant/adjuvant endocrine therapy without disease progression during that treatment and disease-free interval of at least 1 year since the completion of that treatment
* Participants who have bilateral breast cancers which are both HR-positive and HER2-negative
* Confirmation of biomarker eligibility
* Consent to provide fresh or archival tumor tissue specimen
* Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Adequate hematologic and organ function within 14 days prior to initiation of study treatment

Exclusion Criteria:

* Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required
* Metaplastic breast cancer
* Any prior systemic therapy for locally advanced unresectable or metastatic breast cancer
* Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
* Any history of leptomeningeal disease or carcinomatous meningitis
* Known and untreated, or active CNS metastases. Participants with a history of treated CNS metastases are eligible
* Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye
* Symptomatic active lung disease
* History of or active inflammatory bowel disease
* Any active bowel inflammation
* Prior hematopoietic stem cell or bone marrow transplantation
* Treatment with strong cytochrome P450 (CYP) 3A4 inhibitors or strong CYP3A4 inducers within 4 weeks or 5 drug-elimination half-lives, prior to initiation of study treatment

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 7 years)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization to death from any cause (up to 7 years)
measure: Investigator-assessed Objective Response Rate (ORR)
timeFrame: Up to 7 years
measure: Investigator-assessed Duration of Response (DOR)
timeFrame: From the first occurrence of a confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 7 years)
measure: Investigator-assessed Clinical Benefit Rate (CBR)
timeFrame: Up to 7 years
measure: Time to Confirmed Deterioration (TTCD) in Pain
timeFrame: From baseline until end of follow-up (up to 7 years)
measure: TTCD in Physical Function
timeFrame: From baseline until end of follow-up (up to 7 years)
measure: TTCD in Role Function
timeFrame: From baseline until end of follow-up (up to 7 years)
measure: TTCD in Global Health Status
timeFrame: From baseline until end of follow-up (up to 7 years)
measure: Percentage of Participants with Adverse Events
timeFrame: From baseline until end of follow-up (up to 7 years)
measure: Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities Assessed by NCI Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)
timeFrame: Up to 7 years
measure: Number of Participants Reporting Each Response Option for Treatment Side-effect Bother Single-item General Population, Question 5 (GP5) from the Functional Assessment of Cancer Therapy-General Questionnaire; (FACT-G)
timeFrame: Up to 7 years
measure: Change from Baseline in Symptomatic Treatment Toxicities as Assessed Through use of the PRO-CTCAE
timeFrame: Baseline up to 7 years
measure: Change from Baseline in Treatment Side-effect Bother as Assessed Through use of the FACT-G GP5 Item
timeFrame: Baseline up to 7 years
Other outcomes:
Locations:
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers PC - Marietta
state: Georgia
city: Springfield
country: United States
facility: Springfield Clinic
state: Illinois
city: Grand Island
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Salvador
country: Brazil
facility: Obras Sociais Irma Dulce - Osid
state: Bahia
city: Fortaleza
country: Brazil
facility: Crio - Centro Regional Integrado de Oncologia
state: Ceará
city: Vitoria
country: Brazil
facility: Hospital Santa Rita de Cassia Vitoria
state: Espírito Santo
city: Goiania
country: Brazil
facility: Hospital Araujo Jorge
state: Goiás
city: Alfenas
country: Brazil
facility: Centro de Oncologia de Alfenas
state: Minas Gerais
city: Londrina
country: Brazil
facility: Hospital do Câncer de Londrina
state: Paraná
city: Recife
country: Brazil
facility: Hospital do Cancer de Pernambuco - HCP
state: Pernambuco
city: Teresina
country: Brazil
facility: Vencer Oncoclínica - Centro de Pesquisa do Piauí
state: Piauí
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer - INCa
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Beijing City
country: China
facility: Peking Union Medical College Hospital
city: Changsha CITY
country: China
facility: Hunan Cancer Hospital
city: Chengdu City
country: China
facility: West China Hospital - Sichuan University
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
city: Guangzhou
country: China
facility: Sun yat-sen University Cancer Center
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center - Huangpu Campus
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Jiangmen
country: China
facility: Jiangmen Central Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Jinhua City
country: China
facility: Jinhua municipal central hospital
city: Kunming
country: China
facility: Yunnan Cancer Hospital
city: Nanning City
country: China
facility: Guangxi Cancer Hospital of Guangxi Medical University
city: Shantou City
country: China
facility: Shantou Center Hospital
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Tianjin
country: China
facility: Tianjin Cancer hospital Airport hospital
city: Xi'an City
country: China
facility: The Second Affiliated Hospital of Xi'an Jiao Tong University
city: Xian
country: China
facility: Shanxi Provincial People's Hospital
city: Chiayi
country: Taiwan
facility: Chia-Yi Christian Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung Uni Hospital
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Ankara
country: Turkey
facility: Abdurrahman Yurtarslan Onkoloji Training and Research Hospital
city: Ankara
country: Turkey
facility: Ankara City Hospital
city: Bakirkoy / Istanbul
country: Turkey
facility: Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji
city: Istanbul
country: Turkey
facility: Ba?c?lar Medipol Mega Üniversite Hastanesi
city: Mersin
country: Turkey
facility: Mersin City Education and Research Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: