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
3034 - Efficacy and safety of neoadjuvant chemotherapy plus trastuzumab and pertuzumab in non-metastatic HER2-positive breast cancer in real life: NEOPEARL STUDY
Presenter: Maria Agnese Fabbri
Session: Poster Display session 2
Resources:
Abstract
4772 - Real world comparison of the impact of adjuvant capecitabine in women with high-risk triple-negative breast cancer after neoadjuvant chemotherapy
Presenter: Maysa Vilbert
Session: Poster Display session 2
Resources:
Abstract
5627 - Influence of age on the indication of adjuvant chemotherapy in early breast cancer using Oncotype DX. An analysis of 240 patients treated in the Institut Catala d’Oncologia (ICO) hospitals
Presenter: Sabela Recalde
Session: Poster Display session 2
Resources:
Abstract
3917 - Impact of delayed neoadjuvant systemic chemotherapy on survival among breast cancer patients
Presenter: Mariana Chavez Mac Gregor
Session: Poster Display session 2
Resources:
Abstract
2246 - Clinical Confirmation of Higher Exposure to Niraparib in Tumor vs Plasma in Patients With Breast Cancer
Presenter: Laura Spring
Session: Poster Display session 2
Resources:
Abstract
581 - The rationale for the effectiveness of systemic treatment of breast cancer depending on the body weight index
Presenter: Mohammad Hojouj
Session: Poster Display session 2
Resources:
Abstract
5327 - Response to neoadjuvant chemotherapy in HER2 non-overexpressing breast cancer subtypes
Presenter: Silvia Mihaela Ilie
Session: Poster Display session 2
Resources:
Abstract
3613 - Pre-specified interim analysis of the SAFE trial (NCT2236806): a 4-arm randomized, double-blind, controlled study evaluating the efficacy and safety of cardiotoxicity prevention in non-metastatic breast cancer patients treated with anthracyclines with or without trastuzumab.
Presenter: Lorenzo Livi
Session: Poster Display session 2
Resources:
Abstract
3736 - Safety of hypofractionated whole breast irradiation after conservative surgery for patients aged less than 60 years: a multi-center comparative study.
Presenter: Icro Meattini
Session: Poster Display session 2
Resources:
Abstract
5085 - Usefulness of NT-ProBNP as a biomarker of cardiotoxicity in breast cancer patients treated with trastuzumab
Presenter: Isabel Blancas López-Barajas
Session: Poster Display session 2
Resources:
Abstract