P. Aftimos (Brussels, Belgium)
Institute Jules BordetAuthor Of 3 Presentations
Progression after CDK 4/6i: New kids on the block (ID 305)
PI3Kα inhibitors: Addressing unmet needs through precision medicine in HR+, HER2- ABC - From scientific breakthrough to clinical practice (ID 353)
Mentor (ID 380)
Presenter Of 3 Presentations
Mentor (ID 380)
Progression after CDK 4/6i: New kids on the block (ID 305)
PI3Kα inhibitors: Addressing unmet needs through precision medicine in HR+, HER2- ABC - From scientific breakthrough to clinical practice (ID 353)
Author Of 1 Presentation
- E. Agostinetto (Brussels, Belgium)
- M. Paesmans (Brussels, Belgium)
- L. Ameye (Brussels, Belgium)
- I. Veys (Brussels, Belgium)
- L. Buisseret (Brussels, Belgium)
- P. Neven (Leuven, Belgium)
- D. Taylor (Namur, Belgium)
- C. Fontaine (Brussels, Belgium)
- F. Duhoux (Brussels, Belgium)
- J. Canon (Charleroi, Belgium)
- H. Denys (Gent, Belgium)
- F. Coussy (Paris Cedex, France)
- C. Chakiba (Bordeaux, France)
- B. Pistilli (Villejuif, France)
- M. Piccart (Brussels, Belgium)
- M. Ignatiadis (Brussels, Belgium)
- P. Aftimos (Brussels, Belgium)
72TiP - ROSALINE: a phase II, single-arm, neoadjuvant study of targeting ROS1 in combination with endocrine therapy (ET) in invAsive Lobular carcINoma of the brEast
Abstract
Background
Invasive lobular breast cancer (ILBC) is the most common histologic subtype after invasive ductal BC. It is characterized by a distinct clinical course including presentation, sites of metastatic relapse and response rates to conventional therapies. In ILBC, loss of E-cadherin (CDH1) expression is the most frequent oncogenic event (90% of cases). In vivo studies investigating synthetic lethality approaches, have shown profound antitumor effects of ROS1 inhibitors in models of E-cadherin–defective BC, providing the preclinical rationale for assessing their activity in this disease. Entrectinib is a potent small-molecule tyrosine kinase inhibitor that targets TRK, ROS1 and ALK tyrosine kinases. We aim to evaluate the combination of neoadjuvant entrectinib and ET in women with estrogen receptor positive (ER+), HER2-negative (HER2-) early ILBC.
Trial design
Single arm, multi-center, phase II trial testing entrectinib plus ET in pre/post-menopausal patients (pts) with ER+/HER2-, stage II-III (T>20mm, N0/1) ILBC. Pts will receive four 28-day cycles of letrozole (2.5 mg daily) + entrectinib (600 mg daily) +/- goserelin (3.6 mg every 28 days, only in premenopausal pts). Surgery will take place after at least 16 weeks of treatment, during weeks 17−18. Surgery and post-operative therapy will follow local practice. Primary endpoint will be residual cancer burden (RCB) 0/1 rate by local evaluation. Secondary endpoints will include pCR in breast and axilla (ypT0/Tis ypN0), tumor objective response by locally-assessed breast MRI via modified RECIST, and safety. Exploratory analyses on pre- and post-treatment tumor tissue, whole blood and plasma samples will be performed to identify differences between responders and non responders. With a two-step, optimal, Simon design with a one-sided alpha=beta=10%, we defined RCB 0/1 rate of 3% (P0) as minimal required level of activity (target RCB 0/1=15% [P1]). A futility analysis is planned on the first 17 pts. If RCB 0/1 in ≥ 1/17 pts, the study will continue until 39 evaluable subjects are enrolled. If RCB 0/1 in ≥ 3/39 pts, the combination will be considered worthy for further investigation.
Clinical trial identification
NCT04551495.
Legal entity responsible for the study
Institut Jules Bordet, Belgium.
Funding
Roche.
Disclosure
L. Buisseret: Research grant/Funding (institution): AstraZeneca; Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: iTEOS therapeutics; Speaker Bureau/Expert testimony: BMS. D. Taylor: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy: Daiichi Sankyo; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: AstraZeneca. F.P. Duhoux: Research grant/Funding (self), postdoctoral clinical mandate (2017-034) from a not-for-profit organisation: Foundation Against Cancer; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Teva; Speaker Bureau/Expert testimony: Mundi Pharma. H. Denys: Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy: Tesaro; Advisory/Consultancy: GSK; Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: Teva. F. Coussy: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Lilly; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis. B. Pistilli: Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Puma Biotechnology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Novartis; Advisory/Consultancy: Myriad Genetics; Advisory/Consultancy: Pierre Fabre; Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): MSD Oncology; Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Pfizer; Research grant/Funding (self), Research grant/Funding (institution): Daiichi; Research grant/Funding (self), Research grant/Funding (institution): Merus. M. Piccart: Advisory/Consultancy, Board Member (Scientific Board): Oncolytics; Research grant/Funding (institution), Board Member (Scientific Board): Radius; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Camel-IDS; Advisory/Consultancy: Crescendo Biologics; Advisory/Consultancy: DebioPharm; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy: Huya; Advisory/Consultancy: Immunomedics; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Menarini; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Odonate; Advisory/Consultancy: Periphagen; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Seattle genetics; Research grant/Funding (institution): Servier. M. Ignatiadis: Advisory/Consultancy: Celgene; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Tesaro; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Menarini; Research grant/Funding (institution): Silicon Biosystems; Research grant/Funding (institution): Janssen Diagnostics; Travel/Accommodation/Expenses: Amgen. P.G. Aftimos: Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Macrogenics; Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Novartis; Advisory/Consultancy: Amcure; Advisory/Consultancy: Servier; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: Radius; Advisory/Consultancy: Deloitte; Honoraria (self): Synthon; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self): Gilead; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche. All other authors have declared no conflicts of interest.