Abstract 4616
Background
Approximately 40% of pts with HR+, HER2– ABC have mutations (mut) in PIK3CA, which encodes α-PI3K and leads to PI3K pathway hyperactivation and potentially ET resistance. ALP is a selective inhibitor of α-PI3K that, in combination with fulvestrant (FUL), significantly improved median progression-free survival (PFS) vs placebo + FUL in pts with PIK3CA-mut, HR+ HER2– ABC in the phase 3 SOLAR-1 trial (11.0 vs 5.7 mo, respectively; HR 0.65; 95% CI, 0.50-0.85; P < 0.001). BYLieve is an ongoing phase 2, multicenter, open-label, noncomparative study assessing ALP + ET (FUL or letrozole [LET]) in pts with PIK3CA-mut HR+, HER2– ABC who progressed on/after prior treatments (tx).
Trial design
BYLieve includes women (any menopausal status) and men with PIK3CA-mut, HR+, HER2– ABC and evidence of tumor progression on prior tx. Cohorts A and B comprise pts who received a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + ET as their last tx. With the adoption of Amendment 3, a new cohort (C) enrolls pts who had systemic chemotherapy or ET as last prior tx and who failed aromatase inhibitor (AI) in the adjuvant or metastatic setting. In the advanced setting, ≤2 anticancer tx (including ≤1 chemotherapy) are allowed. Pts must have ≥1 measurable lesion per RECIST criteria or ≥ 1 predominantly lytic bone lesion. Key exclusion criteria include prior PI3Ki tx and type 1 or uncontrolled type 2 diabetes. Study tx comprises: Cohort A (prior CDK 4/6i + AI), ALP 300 mg once daily (qd) + FUL 500 mg Q28d + C1d15; Cohort B (prior CDK 4/6i + FUL), ALP 300 mg qd + LET 2.5 mg qd; Cohort C, ALP 300 mg qd + FUL 500 mg Q28d + C1d15. The primary endpoint is the proportion of pts free of progression at 6 mo per local investigator assessment for each cohort. Secondary endpoints include PFS, PFS2, ORR, and CBR. Safety and tolerability will also be assessed, including fasted or random blood glucose levels (non-fasted). Tumor tissue and circulating tumor DNA are collected for biomarker assessments. The study is ongoing and currently recruiting pts, with increase in planned overall enrollment from 160 to 340 pts.
Clinical trial identification
NCT03056755.
Editorial acknowledgement
Medical editorial assistance was provided by Joe Hodgson of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
E. Ciruelos: Advisory / Consultancy, Speaker and consultant fee: Novartis, Roche, Pfzier, Lilly. T. Bachelot: Research grant / Funding (self), Research grant: Novartis; Research grant / Funding (self): Roche; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Pfzier. S. Chia: Advisory / Consultancy, Research grant / Funding (institution), Payment to the institution for conducting clinical trials. Honorarium to myself for advisory boards.: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Payment to the institution for conducting clinical trials. Honorarium to myself for advisory boards.: Pfzier. D. Juric: Advisory / Consultancy, Scientific Advisory Board: Novartis, Genentech, Eisai, Ipsen, EMD Serono. N. Turner: Advisory / Consultancy: AstraZeneca, BMS, Lilly, MSD, Novartis, Pfizer, Roche/Genentech, Tesaro, Bicycle Therapeutics; Research grant / Funding (self): AstraZeneca, BioRad, Pfizer, Roche/Genentech, Clovis, Guardant Health. A. Ridolfi: Full / Part-time employment: Novartis. N. Sophos: Full / Part-time employment: Novartis. B. Cooper: Full / Part-time employment: Novartis. A. Thuerigen: Full / Part-time employment: Novartis. H.S. Rugo: Research grant / Funding (institution): Pfizer, Merck, Novartis, Lilly, Genentech, OBI, Odonate, Daiichi, Eisai, Seattle Genetics and Macrogenics; Travel / Accommodation / Expenses: Lilly, Mylan, Pfizer, Amgen, Merck and Puma. All other authors have declared no conflicts of interest.
Resources from the same session
4732 - Progesterone Receptor Isoform Ratio Dictates Antiprogestins/Progestins Effects on Metastatic Breast Cancer Models
Presenter: Maria Abascal
Session: Poster Display session 2
Resources:
Abstract
5737 - PAM50 and CGH-array genomic characterization of HER2-Equivocal Breast Cancers defined by the 2018 ASCO/CAP recommendations.
Presenter: Carine Ngo
Session: Poster Display session 2
Resources:
Abstract
1096 - OncotypeDX® predictive nomogram for recurrence score output: a machine learning system based on quantitative immunochemistry analysis - ADAPTED01
Presenter: Fabio Marazzi
Session: Poster Display session 2
Resources:
Abstract
5426 - Geriatric parameters predict both disease-related and patient-reported outcomes in older patients with breast cancer
Presenter: Willeke van der Plas-Krijgsman
Session: Poster Display session 2
Resources:
Abstract
5865 - Patients with a 21-gene assay in South East London differ from the TAILORx trial population
Presenter: Charalampos Gousis
Session: Poster Display session 2
Resources:
Abstract
1312 - Predictive tools in adjuvant breast cancer – what is the standard of evidence supporting their utility? A literature review examining validation of Adjuvant!, Cancermath and NHS Predict
Presenter: Alice Loft
Session: Poster Display session 2
Resources:
Abstract
2445 - Oncologic outcome of invasive lobular carcinoma: Is it different from that of invasive ductal carcinoma?
Presenter: Hee Jun Choi
Session: Poster Display session 2
Resources:
Abstract
2476 - Pathologic response and survival efficacy in patients with initial nodal involvement after neoadjuvant chemotherapy in early breast cancer
Presenter: SERAFIN MORALES Murillo
Session: Poster Display session 2
Resources:
Abstract
3761 - Chemotherapy-induced amenorrhea: prognostic impact on premenopausal Egyptian patients with breast cancer
Presenter: Khaled Abdel Karim
Session: Poster Display session 2
Resources:
Abstract
4687 - Predicting the presence of breast cancer using circulating small RNA in the serum
Presenter: Yumiko Koi
Session: Poster Display session 2
Resources:
Abstract