Abstract P1-05-28: Decreases in Circulating Tumor Associated Cells Predicts PFS and OS In A Pooled Analysis Of Phase I Clinical Trials Using SV-BR-1-GM Therapy With Or Without Immune Check-Point Inhibitors In Metastatic Breast Cancer Patients
Authors: Adams Daniel , Chang Mingjin , Lopez-Lago Miguel , Tang Cha-Mei , Williams William , Priore Giuseppe Del 
Published: March 2023

Abstract
Background: In metastatic Breast Cancer (mBC), Circulating Tumor Cells (CTCs) are clinical indicators of worse prognosis and indicate patients (pts) not responding to current therapy. However CTCs are rare, found in &lt; 20% of mBC pts, and many pts without CTCs may also progress. Recently an inflammatory pro-tumorigenic PD-L1 expressing macrophage (Cancer associated macrophage-like cell [CAML])was identified in the blood, which was found in &gt;90% of mBC pts and may indicate tumor response to new therapies (JCO 40[16_Suppl] 2022). SV-BR-1-GM is a mBC cell line derived with antigen presenting characteristics was developed for treatment of mBC as a monotherapy (monoTx), or in combination with checkpoint inhibitors (comboTx). We report preliminary post-hoc results of a pooled analysis of n=18 monoTx mBCs pts and interim results of n=15 comboTx to analyze the predictive value of CTCs & CAMLs, as well as CAML PD-L1 expression, isolated from pt peripheral blood pre & post treatment to predict drug response, with end point outcomes of Progression Free Survival (PFS) and Overall Survival (OS) at 24 months. Methods: The SV-BR-1-GM regimen includes low pre-dose cyclophosphamide, intradermal inoculation of ~20 million irradiated SV-BR-1-GM cells and post-dose local interferon-α with cycles every 2 weeks x 3, then monthly. ComboTx adds an anti-PD-1 antibody with cycles every 3 weeks. Blinded blood samples were taken at baseline (BL), prior to starting SV-BR-1-GM therapy (n=33), and a 2nd sample (T1) taken after therapy initiation (~52 days) obtained as part of the exploratory portion of 2 prospective phase I clinical drug studies, NCT03066947 & NCT03328026, to evaluate the predictive value of CTCs/CAMLs and CAML PD-L1 measured by LifeTracDx liquid biopsy. The quantities of CTCs & CAMLs were analyzed based on PFS using RECIST v1.1 and OS hazard ratios (HRs) by censored univariate analysis at 24 months. Results: A total of 33 mBC pts were pooled from monoTx (n=18), or comboTx (n =15), all with available blood samples at BL. CTCs were found in 30% (n=10/33) of pts at BL, and CAMLs were found in 94% (n=31/33) at BL. Presence of CTCs at BL did not correlate with worse PFS (HR=1.0, p=0.8550), but did trend for pts with worse survival (HR=5.1, p=0.0641). T1 samples were available from 61% (n=20/33) pts. A drop in CAMLs or CTCs after treatment at T1 was observed in 50% of pts, which correlated with a significantly improved PFS HR=11.8, p=0.0019 and OS HR=226.3, p=0.0397. Overall, pts with a decrease in CTCs/CAMLs after induction of SV-BR-1-GM therapy had a ~350% improvement in median PFS (1.9 mo. vs 6.6 mo.) and a ~200% improvement in median OS (6.3 mo. vs 12.4 mo). When stratified between monoTx and comboTx, pts with a decrease in CTCs/CAMLs had an improved PFS (HR 11.9, p=0.0136) in the monoTx group and an improved PFS (HR 17.5, p=0.0017) in the comboTx group. Further, while expression of CAML PDL1 at BL was not correlated with improved PFS (HR=1.0, p=0.9078), CAML PD-L1 expression at BL was correlated with significantly better OS HR=9.5, p=0.0116, consistent with long term benefit of SV-BR-1-GM therapy in this group of pts. Conclusions: We observed that treatment with the SV-BR-1-GM regimen was associated with decreases in the presence of CTCs and CAMLs in 50% of patients, which also significantly correlated with ~350% better median PFS and ~200% better median OS within 2 years. SV-BR-1-GM therapy alone, or as a combination treatment with anti-PD-1, appears to have improved long term clinical outcomes in a large portion of heavily pre-treated mBC patients compared to other typical standard of care published results.
Citation Format: Daniel Adams, Mingjin Chang, Miguel Lopez-Lago, Cha-Mei Tang, William Williams, Giuseppe Del Priore. Decreases in Circulating Tumor Associated Cells Predicts PFS and OS In A Pooled Analysis Of Phase I Clinical Trials Using SV-BR-1-GM Therapy With Or Without Immune Check-Point Inhibitors In Metastatic Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-28.