Abstract OT3-10-01: Phase Ib study of stereotactic radiation and nivolumab in the management of metastatic breast cancer with brain metastases
Authors: Kamran A Ahmed, Youngchul Kim, Avan J. Armaghani, John A. Arrington, Jimmy J. Caudell, Ricardo L. Costa, Brian J. Czerniecki, Arnold B. Etame, Peter A. Forsyth, Hung T. Khong, Sungjune Kim, Loretta Loftus, Timothy J. Robinson, Marilin Rosa, Solmaz Sahebjam, Hatem H. Soliman, Aixa E. Soyano, Nam D. Tran, H. Michael Yu, Hyo S. Han
Journal: Cancer Research (2020)

Abstract Background:Patients with breast cancer brain metastases represent a poor prognosis cohort with a high unmet clinical need. Standard-of-care treatments for patients with breast cancer brain metastases include local treatments, such as surgical resection and radiation treatment modalities that include stereotactic radiosurgery (SRS) or whole brain radiotherapy. Numerous pre-clinical studies have provided evidence to combine radiation therapy with immune checkpoint inhibition to improve response rates. The evidence is strongest for short course, hypofractionated radiation regimens. We hypothesize treatment with nivolumab and SRS will be feasible and well tolerated and may improve intracranial tumor control rates compared to SRS alone. Trial Design:The study is designed as a prospective, single-arm, nonrandomized, open-label, phase Ib trial of nivolumab and SRS among patients with metastatic breast cancer brain metastases. Treatment will be initiated with a dose of nivolumab (480 mg IV) that will be repeated every 4 weeks. The initial dose of nivolumab will be followed 1 week later by SRS at sites of brain metastases or post-operative cavities. Patients will be allowed to continue endocrine and HER2-targeted therapies if brain metastases progression was noted on these agents.Eligibility:Eligible patients include those ≥18, ECOG ≤2 with ≤10 breast cancer brain metastases of all subtypes eligible for stereotactic radiation. Specific Aims:The primary objective is to evaluate the safety and feasibility of nivolumab and SRS to sites of brain metastases. Secondary objectives include evaluation of intracranial progression free survival (PFS), extracranial PFS, overall survival, local control, and distant brain control. Correlative aims include assessing blood and tissue biomarkers (i.e. PD-L1, mutation burden, TCR repertoire etc.) for association with clinical benefit.Statistical Methods:Safety and feasibility will be monitored by a 3 + 3 design followed by a dose expansion phase. Patient Accrual:This study is open with 4 patients enrolled at the time of submission. A total of 12 patients will be enrolled.Contact Information:Kamran A. Ahmed MD, Moffitt Cancer Center, email: kamran.ahmed@moffitt.org, Clinical trial information: NCT03807765. Citation Format: Kamran A Ahmed, Youngchul Kim, Avan J. Armaghani, John A. Arrington, Jimmy J. Caudell, Ricardo L. Costa, Brian J. Czerniecki, Arnold B. Etame, Peter A. Forsyth, Hung T. Khong, Sungjune Kim, Loretta Loftus, Timothy J. Robinson, Marilin Rosa, Solmaz Sahebjam, Hatem H. Soliman, Aixa E. Soyano, Nam D. Tran, H. Michael Yu, Hyo S. Han. Phase Ib study of stereotactic radiation and nivolumab in the management of metastatic breast cancer with brain metastases [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-10-01.