Abstract 158TiP
Background
In SOLAR-1 trial (NCT02437318), patients (pts) with HR+/HER2–, PIK3CA-mutated ABC treated with alpelisib + fulvestrant showed a prolonged progression free survival (PFS) vs pts treated with fulvestrant alone who were previously treated with a CDK4/6 inhibitor (9 pts). Additional biomolecular data would be useful to help clinicians in defining an optimal personalized treatment strategy.
Trial design
BioItaLEE, a phase IIIb, open-label, Italian, multicenter study (NCT03439046) includes two phases: a core phase that enrolled 287 postmenopausal pts with HR+, HER2– ABC treated in first-line with ribociclib + letrozole and an extension phase (introduced by a protocol amendment), which is now enrolling PIK3CA-mutated pts who had progressed on the core phase and now they will be treated in second-line with alpelisib and fulvestrant. Here, we present the extension phase trial design and its current status. Similar to the core phase, biological samples will be prospectively collected at different time points as follows: liquid biopsies at baseline, cycle 1 day 15, cycle 2 day 1, at first imaging evaluation, and upon disease progression; and also newly obtained tissue biopsies at baseline, and at progression. The primary objective is to identify the circulating tumor DNA (ctDNA) alterations at baseline, to describe their evolution during treatment, and to evaluate the association with clinical outcome. An optimized next-generation sequencing approach for the detection of low abundance events in ctDNA is adopted. The secondary objectives include the evaluation of ctDNA alterations at time of tumor progression, tumor microenvironment, PFS on second-line treatment, clinical efficacy and safety. The exploratory objectives include pharmacogenomics and drug-drug interactions. A descriptive statistics will be applied. The first extension phase patient was screened on September 4, 2019, and as of April 2020, 10 PIK3CA-mutated pts have been enrolled. Enrollment is ongoing.
Clinical trial identification
NCT03439046.
Editorial acknowledgement
Legal entity responsible for the study
Novartis Farma SpA, Origgio, Italy.
Funding
Novartis Farma SpA, Origgio, Italy.
Disclosure
L. Del Mastro: Honoraria (self), Personal fees: Roche; Honoraria (self), Personal fees: Pfizer; Honoraria (self), Personal fees: Ipsen; Honoraria (self), Personal fees: Eli Lilly; Honoraria (self), Personal fees: Novartis; Honoraria (self), Personal fees: Takeda; Honoraria (self), Personal fees: MSD; Honoraria (self), Personal fees: Genomic Health; Honoraria (self), Personal fees: Celgene; Honoraria (self), Personal fees: Seattle Genetics. C. Zamagni: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Grant, personal fees and non-financial support: Roche; Advisory/Consultancy, Grant: Eisai; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses, Grant, personal fees and non-financial support: Novartis; Advisory/Consultancy, Research grant/Funding (self), Grant, personal fees and non-financial support: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses, Grant, personal fees and non-financial support: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses, Grant: PharmaMar; Advisory/Consultancy, Travel/Accommodation/Expenses, Grant: Celgene; Advisory/Consultancy, Grant: Lilly; Advisory/Consultancy, Grant, personal fees: Amgen; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Grant, personal fees: Tesaro; Advisory/Consultancy, Personal fees: QuintikesIMS; Research grant/Funding (institution), Travel/Accommodation/Expenses, Grant: PierreFabre; Research grant/Funding (institution), Travel/Accommodation/Expenses, Grant: Istituto Gentili; Research grant/Funding (institution), Grant: Takeda; Research grant/Funding (institution), Grant: TEVA; Research grant/Funding (institution), Grant: Medivation; Research grant/Funding (institution), Grant: Abbvie; Research grant/Funding (institution), Grant: Array BioPharma; Research grant/Funding (institution), Grant: Morphotek; Research grant/Funding (institution), Grant: Synthon; Research grant/Funding (institution), Grant: Seattle Genetics. V. Guarneri: Advisory/Consultancy, Speaker Bureau/Expert testimony, Personal fees: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Personal fees: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Grant, personal fees: Roche. F. Puglisi: Honoraria (self), Personal fees: Amgen; Research grant/Funding (institution), Grant: Astrazeneca; Travel/Accommodation/Expenses, Others: Celgene; Research grant/Funding (institution), Grant, others: Eisai; Research grant/Funding (institution): Eli Lilly; Honoraria (self), Personal fees: MSD; Honoraria (self), Personal fees: Novartis; Honoraria (self), Personal fees: Pierre-Fabre; Research grant/Funding (institution), Travel/Accommodation/Expenses, Grant, personal fees and other: Roche; Honoraria (self), Grant: Takeda. M.A. Colleoni: Advisory/Consultancy, Personal fees: Novartis. F. Montemurro: Honoraria (self), Personal fees: Novartis; Honoraria (self), Personal fees: Roche; Honoraria (self), Personal fees: Pfizer; Honoraria (self), Personal fees: Eli Lilly; Honoraria (self), Personal fees: Daiichi Sankyo; Honoraria (self), Personal fees: Pierre Fabre. A. Zambelli: Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Eli Lilly; Honoraria (self): Roche; Honoraria (self): AstraZeneca. G. Bianchi: Advisory/Consultancy, Personal fees: Novartis; Advisory/Consultancy, Personal fees: Eli Lilly. D. Castelletti: Full/Part-time employment: Novartis. G. Arpino: Honoraria (self), Grant, personal fees: Roche; Honoraria (self), Personal fees: Lilly; Honoraria (self), Grant, personal fees, non-financial support: Pfizer; Honoraria (self), Personal fees: Amgen; Honoraria (self), Grant, personal fees: Eisai; Advisory/Consultancy, Personal fees, non-financial support: Novartis. All other authors have declared no conflicts of interest.