Abstract
Introduction Transforming "cold" tumors into "hot" ones is critical for the success of immuno-oncology therapies, but there has been little evidence that “cold” tumors can be turned “hot”. SV-BR-1-GM, an allogenic human cancer cell line (Bria-IMT) with antigen-presenting capabilities, is designed to counteract the immunosuppressive tumor microenvironment. Zr-89 crefmirlimab berdoxam is a radio-labeled truncated mini-antibody specific to human CD8α developed for CD8 ImmunoPET imaging. We conducted CD8 imaging before and after Bria-IMT treatment to evaluate baseline and subsequent intra-lesional changes in CD8+ T cell tumor infiltration. We now present additional data from the nested feasibility trial of immunoPET in late state MBC. Methods Nested feasibility trial of subjects from two CD8 immunoPET capable tertiary care sites participating in NCT03328026 a randomized phase 2 of Bria-IMT in combination with a check point inhibitor (CPI). Standard Uptake Value (SUV) was evaluated pre-dose and following therapy. Results 6 patients, median age 60.5 (44-66), enrolled in the ongoing Bria-IMT trial in advanced heavily pretreated metastatic breast cancer. Median number of prior therapies was 7 (4-8). Prior lines included antibody-drug conjugates (ADCs) and CPIs. All patients had progressed on prior treatment. Four of these patients were randomized to start the CPI after 2 cycles of Bria-IMT to “train” the host immune system before adding the CPI; 2 patients were randomized to begin CPI concurrent in C1 with Bria-IMT. Four patients matched at least 2 SV-BR-1-GM HLA loci, which in previous publications is associated with greater clinical benefit. Sites of disease included in situ breast mass, multiple lymph nodes, visceral and osseous metastases. On follow-up ImmunoPET, each patient demonstrated an increase in SUV in at least one metastatic lesion (range –57.4 - 442.9%) including lung, soft tissue, liver, lymph node, dural based and bony metastases. There was no consistent change recognized in any of these groups except as noted below. Evaluable subjects with HLA matches (3/4) did not experience any increases in CD8+ ImmunoPET SUV at inguinal lymphatic sites while those without HLA matches (n=2) showed increase in CD8 SUV at these sites. In addition, bilateral axillary lymph nodes presented with a median SUV of 6.4 (1.4 - 15.1) after treatment as compared to a median SUV of 7.4 (2.1-18.9) at baseline. 3 out of the 6 patients showed a decrease in neutrophil/lymphocyte ratio NLR at cycle 2 when compared to baseline values. The longest survivor on trial (>1yr, after 6 prior lines, ER/PR +, HER2+) CD8 PET also had the largest percentage (442.9%) increase of any patient in SUV (right frontal dural based). This lesion completely resolved around cycle 8. Additional correlation with tumor genomics will be reported. Conclusion We report additional data supporting future hypotheses and that "cold" tumors can become "hot" when treated with Bria-IMT in combination with an anti-PD-1 CPI, as demonstrated by metastatic site-specific CD8+ PET results. Subjects in a now nearly completed randomized phase 2 demonstrated responses of metastatic lesions on CD8 ImmunoPET. The nonspecific nodal localization of CD8 ImmunoPET may indicate a systemic activation of CD8 positive lymphoid cells in response to peripheral non-lesional SV-BR-1-GM injections. These results suggest a potential value of CD8 ImmunoPET in identifying lesions that are progressing on treatment versus pseudo progression. It also provides support that the Bria-IMT combination immune-based therapy can result in an increase of CD8+ tumor infiltrating lymphocytes in breast cancer metastatic sites as well as in lymphoid organs. This advance may aid in triaging patients, adjudicating pseudo-progression and predicting clinical benefit of immune based therapies.
Citation Format: Ephraim Parent, Carmen Calfa, Saranya Chumsri, Blaise Bayer, Tamar Aghajanian, Giuseppe Del Priore, William Williams, Russ Kuker. Bria-IMT CD8+ Tumor Infiltrating Lymphocytes Turn “Cold” Tumor “Hot” in Metastatic Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-10-12.