Neoadjuvant Study of Targeting ROS1 in Combination With Endocrine Therapy in Invasive Lobular Carcinoma of the Breast (ROSALINE)

• Status: Recruiting
• Trial end date: 2023-03-01

Summary

Despite different clinical characteristics including the response to treatment and the patterns of metastatic relapse, invasive lobular breast carcinoma (ILBC) is treated like invasive ductal breast carcinoma (IDBC) carcinoma both in the clinics and in clinical trials. A large majority of ILBC are ER+/HER2- and almost 90% have loss of E-cadherin (CDH1) expression. A non-clinical study of CDH1 synthetic lethality interactions has identified ROS1 as a potential target. In vivo, ROS1 inhibitors produced profound antitumor effects in multiple models of E-cadherin-defective breast cancer, providing the preclinical rationale for assessing ROS1 inhibitors in this setting. Endocrine therapy being the mainstay of therapy for ER+/HER2- ILBC and the pre-operative setting offering a platform for rapid drug evaluation and biomarker research, the ROSALINE phase 2 study will evaluate the efficacy of Entrectinib (a potent inhibitor of ROS1 among other targets) in combination with letrozole (+ goserelin in premenopausal women) in the early setting of ILBC (stages 1 to 3). The neoadjuvant therapy will last 4 months and post-operative therapy will follow local practice. Biomarker research will include RNA sequencing of initial biopsis and surgical specimens, as well as liquid biopsies.

• Phase: Phase 2

Details

• Lead Sponsor: Jules Bordet Institute
• Collaborator: Hoffmann-La Roche
• Treatments: Entrectinib; Goserelin; Letrozole