Abstract 266P
Background
MEN1611 (MEN) is an oral PI3K inhibitor active on the p110α mut and WT, β and γ isoforms, while sparing the δ. B-PRECISE-01 is an ongoing phase 1b study investigating MEN in combination with T ± F. No dose-limiting toxicities (DLTs) were observed during the escalation step and MEN 48 mg BID was selected as Recommended Phase 2 Dose (R2PD) for cohort expansion (CE).
Methods
In this open-label, 2-arm study, eligible patients (pts) had HER2+/PIK3CAmut locally unresectable advanced or metastatic (a/m) BC and were treated with at least 2 prior anti-HER2 therapies in the metastatic setting including T. All pts received MEN+T, while F was added in hormone receptor positive (HR+) postmenopausal women. Pooled safety and efficacy data from the two subpopulations of CE are presented herein.
Results
As of March 2021, 42 female pts were treated: 36 of them with MEN 48 mg BID (18 MEN+T and 18 MEN+T+F). Median age 55 years (range 34-78), 25% premenopausal, ECOG PS 0-1: 95.2%. Median metastatic regimes 4; 57.1% had prior pertuzumab and 73.8% had prior T-DM1. Common treatment-emergent adverse events (TEAEs, ≥20%) were diarrhea 64.3%, nausea 42.8%, asthenia 31%, decreased appetite 28.6%, anemia 28.6%, and hyperglycemia 23.8%. Most treatment-related AE (TRAEs) were reversible and manageable by supportive care. TRAEs caused treatment interruption in 14 pts (33.3%, 1 pt definitely) and dose reduction in 6 pts (16.7%, only allowed in CE) mostly hyperglycemia, diarrhea, nausea, asthenia and decreased appetite. Serious TRAEs were experienced by 8 pts (19%): hyperglycemia 3 pts, diarrhea 2 pts, general physical health deterioration, generalized edema, and pneumonitis (1 pt each). In the efficacy-evaluable population (n=29) 9 pts showed partial response (MEN+T 4/11, MEN+T+F 5/18), and 18 pts had stable disease (MEN+T 6/11, MEN+T+F 10/18) as best response. Seven pts were on treatment > 6 months (MEN+T 3, MEN+T+F 4), and 1 pt received MEN+T > 12 months.
Conclusions
MEN combined with T ± F shows a manageable safety profile with encouraging duration of antitumoral activity in heavily pre-treated pts with HER2+/PIK3CAmut a/m BC. Recruitment for CE is open.
Clinical trial identification
NCT03767335, MEN1611-01, EudraCT 2017-004631-36.
Editorial acknowledgement
Legal entity responsible for the study
Menarini Ricerche S.p.A.
Funding
Menarini Ricerche S.p.A.
Disclosure
M. Piccart: Financial Interests, Institutional, Other, Role: Board Member (Scientific Board): Oncolytics; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): AstraZeneca; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): Camel-IDS; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): Immunomedics; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): Lilly; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): MSD; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): Novartis; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): Odonate; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): Pfizer; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): Roche-Genentech; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): Seattle Genetics; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): Immutep; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): Seagen; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): NBE Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Radius; Financial Interests, Institutional, Research Grant: Roche-Genentech; Financial Interests, Institutional, Research Grant: Servier; Financial Interests, Institutional, Research Grant: Synthon; Financial Interests, Institutional, Advisory Role, Consultant (honoraria): Menarini; Financial Interests, Institutional, Research Grant: Menarini. H. Arkenau: Financial Interests, Institutional, Full or part-time Employment: HCA Sarah Cannon; Financial Interests, Institutional, Other, Honoraria: Roche; Financial Interests, Institutional, Other, Honoraria: Ionctura; Financial Interests, Institutional, Other, Honoraria: Boyer; Financial Interests, Institutional, Other, Honoraria: Bicycle; Financial Interests, Institutional, Other, Honoraria: Servier; Financial Interests, Institutional, Other, Honoraria: Guardant; Financial Interests, Institutional, Other, Research funding: HCA Sarah Cannon. S.I. Escrivá-de-Romaní: Financial Interests, Personal and Institutional, Invited Speaker: Roche; Financial Interests, Personal and Institutional, Advisory Board: Roche; Financial Interests, Personal and Institutional, Other, Grants for the institution: Roche; Financial Interests, Personal and Institutional, Other, Travel Grants: Roche; Financial Interests, Personal, Invited Speaker: Daiichi Sankio; Financial Interests, Personal, Advisory Board: Daiichi Sankio; Financial Interests, Personal, Other, Travel Grants: Daiichi Sankio; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Other, Travel Grants: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Other, Grants for the institution: Synthon; Financial Interests, Institutional, Other, Grants for the institution: Zymeworks. S.J. Howell: Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Advisory Board: Genomic Health. B. Jimenez-Rodriguez: Financial Interests, Personal, Invited Speaker: Lilly. M. Palleschi: Financial Interests, Institutional, Advisory Board: Novartis. F. Duhoux: Financial Interests, Institutional, Advisory Role: Roche; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Lilly; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: Amgen; Financial Interests, Institutional, Advisory Role: Daiichi Sankyo; Financial Interests, Institutional, Advisory Role: Pierre Fabre; Other, Institutional, Other, Travel, accommodation, expenses: Amgen; Other, Institutional, Other, Travel, accommodation, expenses: Roche; Other, Institutional, Other, Travel, accommodation, expenses: Teva; Other, Institutional, Other, Travel, accommodation, expenses: Pfizer. G. Curigliano: Financial Interests, Institutional, Advisory Role, Consulting fee: BMS; Financial Interests, Institutional, Advisory Role, Consulting fee: Seagen; Financial Interests, Institutional, Advisory Role, Consulting fee: AstraZeneca; Financial Interests, Institutional, Advisory Role, Consulting fee: Pfizer; Financial Interests, Institutional, Advisory Role, Consulting fee: Lilly; Financial Interests, Institutional, Advisory Role, Consulting fee: Novartis; Financial Interests, Institutional, Advisory Role, Consulting fee: Veracyte; Financial Interests, Institutional, Advisory Role, Consulting fee: Daiichi Sankyo; Financial Interests, Institutional, Advisory Role, Consulting fee: Roche; Financial Interests, Institutional, Other, Honoraria: Pfizer; Financial Interests, Institutional, Other, Honoraria: Lilly; Financial Interests, Institutional, Other, Honoraria: Novartis; Financial Interests, Institutional, Other, Honoraria: Daiichi Sankyo; Other, Institutional, Other, Support for attending meetings and/or travel: Roche; Other, Institutional, Other, Support for attending meetings and/or travel: Pfizer. P.G. Aftimos: Financial Interests, Institutional, Advisory Role, Consulting: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role, Consulting: Macrogenics; Financial Interests, Institutional, Advisory Role, Consulting: Roche; Financial Interests, Institutional, Advisory Role, Consulting: Novartis; Financial Interests, Institutional, Advisory Role, Consulting: Amcure; Financial Interests, Institutional, Advisory Role, Consulting: Servier; Financial Interests, Institutional, Advisory Role, Consulting: G1 Therapeutics; Financial Interests, Institutional, Advisory Role, Consulting: Radius; Financial Interests, Institutional, Advisory Role, Consulting: Deloitte; Financial Interests, Institutional, Other, Honoraria: Synthon; Financial Interests, Institutional, Other, Honoraria: Amgen; Financial Interests, Institutional, Other, Honoraria: Novartis; Financial Interests, Institutional, Other, Honoraria: Gilead; Other, Institutional, Other, Travel grants: Amgen; Other, Institutional, Other, Travel grants: MSD; Other, Institutional, Other, Travel grants: Pfizer; Other, Institutional, Other, Travel grants: Roche; Financial Interests, Institutional, Research Grant, Research funding to my institution: Roche. H. Wildiers: Financial Interests, Institutional, Advisory Role, Consultancy fee: AbbVie; Financial Interests, Institutional, Invited Speaker: Ariez; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Biocartis; Financial Interests, Institutional, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Expert Testimony: DNA Prime; Financial Interests, Institutional, Advisory Board: Eisai; Financial Interests, Institutional, Other, Consultancy fee: Immutep Pty; Financial Interests, Institutional, Advisory Board: KCE; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Orion corporation; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: PSI Cro AG; Financial Interests, Institutional, Advisory Board: Puma Biotechnology; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: Syrtex; Financial Interests, Institutional, Research Grant, Grant to institute to perform a multicentric national academic trial: Novartis; Financial Interests, Institutional, Research Grant, Grant to the Leuven Breast Center to support the research database: Roche; Other, Institutional, Other, Travel and accommodations: Pfizer; Other, Institutional, Other, Travel and accommodations: Roche. F. Amair-Pinedo: Financial Interests, Institutional, Full or part-time Employment: Menarini Ricerche S.p.A. A.U.E. Pellacani: Financial Interests, Institutional, Full or part-time Employment: Menarini Ricerche S.p.A. D.O. Laurent: Financial Interests, Institutional, Full or part-time Employment, Menarini Employee: Berlin Chemie/Menarini Ricerche Spa. All other authors have declared no conflicts of interest.