Eligible patients: Patients must be 18 years or older with confirmed Estrogen receptor positive (>1%), progesterone receptor positive or negative, and HER2-negative Metastatic (Stage IV) Lobular breast Cancer.  Participant must have been exposed to a CDK4/6i prior to enrollment. Patients must be willing to undergo a biopsy if the tumor is safely accessible. If a biopsy is not feasible, pre-treatment archival tissue is acceptable. Unlimited prior hormonal and targeted therapy and up to 2 prior chemotherapy or ADC agents allowed. Bone only disease allowed if primarily lytic in nature. Repotrectinib is given orally and Fulvestrant are subcutaneous injections.
Cohort 1 Repotrectinib plus Fulvestrant. Patients must not have been exposed to prior Fulvestrant.
Cohort 2: (after Cohort 1 accrual): Single agent Repotrectinib including those who have had prior exposure to Fulvestrant.
Description of Trial/Summary: To determine if the combination of Repotrectinib and Fulvestrant or Repotrectinib monotherapy can control the disease in participants with metastatic invasive lobular carcinoma.
Background: Repotrectinib is in a class of medications called kinase inhibitors and has been FDA approved for locally advanced or metastatic non-small cell lung cancer (NSCLC) with excellent clinical activity and well tolerated side effects. Repotrectinib acts to inactivate the ROS-1 protein. An earlier generation of a ROS1 inhibitor called Crizotinitib in mILC called Rolo has finished accrual and being studied in the UK.
Why is this study beneficial?/Important? This trial is the first treatment trial for Metastatic lobular patients in the United States. This trial will test whether a drug called Repotrectinib can target a specific weak spot in lobular breast cancer. Lobular breast cancers are missing a protein called E-Cadherin, which normally helps cells stick together. When E-Cadherin isn’t working properly, the cancer cells become more dependent on another protein called ROS1 to survive. Repotrectinib blocks ROS1, and early laboratory studies have shown that lobular cancer cells can’t survive when both E-Cadherin and ROS1 are missing. This makes Repotrectinib a promising treatment for patients with lobular breast cancer.
Principal Investigator: Jason A. Mouabbi MD Assistant Professor | Breast Medical Oncology , MD Anderson, Cancer Center, Houston, Texas
Trial Contact(s):
Toni Zaayman:Â tizaayman@mdanderson.org, 832-546-7723
Livia Geoffrey:Â lgeoffrey@mdanderson.org
Trial Location(s): MD Anderson Cancer Center, Houston, Texas
Time Commitment: Every 4 weeks for approximately 1 year
More Information:Â
Clinical Trials.gov: https://clinicaltrials.gov/study/NCT06408168?term=REPLOT&rank=1#more-information
MD Anderson Website: https://www.mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2024-0099.html
