Differential efficacy of SV-BR-1-GM in inducing intracranial metastasis regression.
Authors: Kamaraju Sailaja , Chumsri Saranya , Bayer Blaise , Chang Mingjin , Williams William , Wiseman Charles L. , Del Priore Giuseppe 
Published: July 2024

e13119

Background: Breast cancer metastasis to the central nervous system (CNS) and intracranial area often leads to severe morbidity and mortality. While systemic treatments manage systemic tumors, their impact on CNS/intracranial metastases is limited. Cell based therapies like SV-BR-1-GM may overcome this limitation. SV-BR-1-GM is a GM-CSF secreting, antigen-presenting immortalized breast cancer cell line. We report its efficacy on CNS tumor regression. Methods: Post-hoc analysis of a subset of all advanced MBC patients with CNS/intracranial metastases from previous phase 1, 2, and an ongoing randomized phase 2, trials (n=7 subjects) of SV-BR-1-GM. Bria-IMT monotherapy (intradermal SV-BR-1-GM + cyclophosphamide 300 mg/m2, +interferon-alpha) was administered q3wks to 2 subjects; an immune checkpoint inhibitor (ICI) was administered with each cycle in the combination setting (n=5). Results: There were 7 patients with intracranial metastases at baseline of whom 5 had intracranial tumor responses. Of the 5 responders, median pt age = 66 (range 58-70), median prior lines = 5.5 (3-13), and median time from initial diagnosis = 7.5 years (3-10). 4/5 pts had ≥1 HLA class match with SV-BR-1-GM. 3 were HR + and 1 HER2 +. Pt A002 (ER+/PR+, HER2-) received 6/6 planned cycles, achieving an 83% reduction in breast lesions; after 3 months off therapy, imaging revealed multiple brain metastases and recurrence of right breast lesions. Following 3 additional cycles there was marked regression in both brain and breast lesions. Pt 02-003 (ER-/PR-, HER2 1+ (IHC)) received 5 cycles of SV-BR-1-GM and observed a 60% reduction (5mm -> 2mm) in a left parietal periventricular lesion, and complete resolution (CR) of a left parietal lobe. Pt 06-005 (ER+/PR-, HER2 1+) demonstrated a 56% (9mm -> 4mm) reduction in the thickness of a dural lesion overlying the left anterior temporal lobe after 6 cycles of SV-BR-1-GM + ICI. After 2 additional cycles of SV-BR-1-GM + ICI and 1 cycle of SV-BR-1-GM (ICI skipped on final cycle due to grade 2 AE), patient achieved CR of a left orbital mass observed at baseline (24mm -> 0m). Pt06-007’s (ER-/PR-, HER2 1+) CNS lesions showed a median reduction of 49% compared to baseline after 3 cycles. Pt 11-018 (ER+/PR-, HER2 +) showed standard progression (SD) at initial restaging; 14% increase in sum of diameters of intracranial metastasis. Subsequent imaging, after 3 cycles, showed significant orbital tumor reduction along with reported improvement in eye pain. Conclusions: This post-hoc analysis demonstrated promising efficacy of the Bria-IMT regimen either alone or in combination with ICIs in CNS/intracranial metastasis. The CNS/intracranial regression seen across all breast cancer subtypes among heavily pretreated patients highlights the potential of SV-BR-1-GM in managing CNS metastasis. Ongoing trials will further evaluate the efficacy of the Bria-IMT regimen in patients with CNS/intracranial metastasis. Clinical trial information: NCT03328026 .