Resumen

The purpose of this study was to determine whether treatment with alpelisib in combination with nab-paclitaxel is safe and effective in subjects with advanced triple negative breast cancer (aTNBC) who carry either a PIK3CA mutation (Study Part A) or have PTEN loss (Study Part B1) or PTEN loss without PIK3CA mutation (Study Part B2)

Descripción detallada

The recruitment of Part A was halted on 11-Nov-2022 due to slow recruitment. Since Part B1 did not meet its primary objective for confirmed overall response rate, the Part B2 was not initiated, and the recruitment was halted for the entire study. Upon confirming either PIK3CA mutation and/or PTEN loss status, advanced TNBC participants meeting all other eligibility criteria were assigned to either Part A (PIK3CA mutation regardless of PTEN loss) or Part B1 (PTEN loss with PIK3CA unknown or non-mutant). In Part A, participants were randomized a 1:1 to receive either: * alpelisib 300 mg daily orally + nab-paclitaxel 100 mg/m\^2 intravenously (IV) on Days 1, 8, and 15 of each 28-day cycle or * placebo + nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle. In Part B1, participants received alpelisib 300 mg daily orally + nab-paclitaxel 100 mg/m\^2 IV on Days 1, 8, and 15 of each 28-day cycle.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 100 YearsSexo: ALL

Criterios de inclusión

Participant has histologically confirmed diagnosis of advanced (loco-regionally recurrent and not amenable to curative therapy), or metastatic (stage IV) TNBC
Participant has either a measurable disease per RECIST 1.1 criteria or, if no measurable disease is present, then at least one predominantly lytic bone lesion or mixed lytic-blastic bone lesion with identifiable soft tissue component (that can be evaluated by CT/MRI) must be present. Part B1: Participants must have measurable disease
Participant has adequate tumor tissue to identify the PIK3CA mutation status (either carrying a mutation or without a mutation) and the PTEN loss status; both of which will determine whether the subject can be allocated to Part A - PIK3CA mutation regardless of PTEN status; or to Part B1 - PTEN loss or to Part B2 - PTEN loss without a PIK3CA mutation
Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Participant has received no more than one line of therapy for metastatic disease
Participant has adequate bone marrow and organ function

Criterios de exclusión

Participant has received prior treatment with any PI3K, mTOR or AKT inhibitor
Participant has a known hypersensitivity to alpelisib, nab-paclitaxel or to any of their excipients
Participant has not recovered from all toxicities related to prior anticancer therapies to NCI CTCAE version 4.03 Grade ≤1; with the exception of alopecia
Participant has central nervous system (CNS) involvement which was not previously treated and/or was newly detected at screening
Participant with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on Fasting Plasma Glucose and HbA1c
Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) based on investigator discretion
Participant has a history of acute pancreatitis within 1 year prior to screening or past medical history of chronic pancreatitis
Participant has currently documented pneumonitis/interstitial lung disease
Participant has a history of severe cutaneous reactions, such as Steven-Johnson Syndrome (SJS), erythema multiforme (EM),Toxic Epidermal Necrolysis (TEN) or Drug Reaction with Eosinophilia and Systemic Syndrome (DRESS)
Participant with unresolved osteonecrosis of the jaw

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

alpelisib

placebo

nab-paclitaxel

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores