Salgado, Marcela

TPS1138 Background: The SV-BR-1-GM breast cancer cell line activates anti-tumor immunity by expressing tumor associated antigens and secreting GM-CSF which enhances dendritic cell activation and promotes adaptive (T-cell mediated) and innate (dendritic and NK cell) immune responses. The cells are also engineered to optimize immune recognition through pt specific HLA antigen matching. SV-BR-1-GM acts through direct antigen presentation and CD4+ T-cell activation and, when combined w/ checkpoint inhibitors (CPIs), has demonstrated clinical benefit in 54 heavily pretreated metastatic breast cancer (MBC) pts. In pts w/ disease progression following CPI therapy, similar or improved progression free survival (PFS) compared to their prior treatment regimen. Disease control following antibody drug conjugates was observed in 40%of pts. Clinical benefit was seen in 5 out of 8 pts w/ untreated intracranial metastases. CD8+ Immuno-PET imaging suggests systemic activation, w/ increased CD8+ tumor infiltrating lymphocytes at both primary and metastatic tumor sites, as well as lymphoid organs. Optimized sequencing of CPI w/ SV-BR-1-GM and its latest phase 3 formulation have shown enhanced clinical outcomes, including improved overall survival (OS) (median 13.4 mos), PFS (3.6 mos), and clinical benefit rate (CBR; 61%).These findings have informed refinements to the ongoing pivotal, registration enabling Phase 3 trial, designed to optimize pt selection and treatment sequencing strategies. Methods: This ongoing multicenter, randomized, open label Phase 3 trial evaluates Bria-IMT + CPI vs. Treatment of Physician’s Choice (TPC) in MBC pts lacking approved curative therapies. Pts are randomized 1:1:1 to Bria-IMT + CPI, TPC, or Bria-IMT monotherapy (discontinued after 150 enrollments to prioritize combination arms). The Bria-IMT regimen consists of: Day -2: Cyclophosphamide 300 mg/m², Day 0: 20M irradiated SV-BR-1-GM cells, Day 2/3: 0.1 mcg pegylated α interferon at each inoculation site. CPI infusion is administered Day -3 to 3. Cycles q3w. TPC regimens follow site specific SOC. Imaging q6w (first 2 cycles), then q8w. Eligibility includes all MBC subtypes, including CNS mets, and permits prior CPI therapy ( >21 days pre-treatment). There will be 100 sites across the U.S., Canada, and ex-North America w/ an enrollment target of 404. The trial is currently active at 59 sites with 217 sub investigators. To date, 67 pts screened: 46 randomized (median age 56 yrs [34–83], median 6 [2–13] prior lines of therapy. The primary endpoint is OS, with an interim analysis at 144 events targeting a hazard ratio of 0.6. Secondary endpoints: PFS, overall response rate, CBR, CNS event free survival, and TWiST. Safety analyses ongoing; pt reported outcomes assess subjective treatment impact. Clinical trial information: NCT03328026 .

1096 Background: Bria-IMT is a combination immunotherapy consisting of allogeneic whole cell cancer vaccine (SV-BR-1-GM) administered w/ immune checkpoint inhibitor (CPI). SV-BR-1-GM breast cancer cells are engineered to directly stimulate anti tumor immunity via expression of tumor associated antigens and secretion of GM-CSF to enhance dendritic cell activation. Addition of CPI potentiates SV-BR-1-GM to overcome the immune suppressive tumor microenvironment. Methods: This Ph I/randomized Ph II study evaluated the Bria-IMT regimen in pts w/ metastatic breast cancer; CTX (300 mg/m²) on day -2/-3, SV-BR-1-GM and CPI on Day 0, w/ low dose peg interferon α at inoculation sites on day 2 (±1) . Phase II pts were randomized 1:1 to receive CPI at cycle 1 or cycle 2. Two SV-BR-1-GM formulations (w/ vs w/o IFNγ incubation) were evaluated. Biomarkers included cancer-associated macrophage-like cells, circulating tumor cells, PD-L1 scores, and delayed-type hypersensitivity skin tests. Results: 54 pts (22 Ph I, 32 Ph II) enrolled; 11 received pembrolizumab, 44 retifanlimab (1 crossover). 33 (61%) pts were ER+/PR+/HER2-, 18 (33%) TNBC, 3 (6%) HER2+. Median OS, PFS, ORR, and CBR were evaluated against two pivotal Ph 3 trials, ASCENT 1 (SG in TNBC) and TROPiCS-02 2 (SG in HR+/HER2- MBC) (see Table 1). In randomized pts, C1 vs C2 CPI had PFS (3.7 vs 3.2 mos, P=0.09) and OS (11.4 vs 7.4 mos, P=0.19). Pts receiving Ph 3 formulation (w/o IFNγ; N=37) had greater PFS (3.6 vs 2.6 mos, P=0.01) and OS (13.4 vs 6.9 mos, P=0.01). Bria-IMT was well tolerated w/ no Tx related D/Cs. Conclusions: The Bria-IMT Ph 3 formulation cohort OS was comparable to ASCENT and TROPiCS-02 (13.43 vs 11.8, 14.4 mos), exceeding TPC arms (6.9, 11.2 mos). CBR (61%) compared favorably to ASCENT (40%) and TROPiCS-02 (34%); ORR (14%) matched or exceeded TPC arms (4%, 14%). These outcomes were observed in a more heavily pretreated population, demonstrating Bria-IMT’s clinical activity. Randomized Ph 2 results suggest efficacy and safety in heavily pretreated MBC, w/ no significant OS difference between C1 and C2 CPI initiation and 22% of pts still in active survival follow up. Superior outcomes w/ the Ph 3 formulation support its continued evaluation. A randomized Ph 3 trial is ongoing, comparing Bria-IMT vs treatment of physician’s choice (NCT06072612). Clinical trial information: NCT03328026 . Trial (Cohort) Age (Median, Range) Prior Therapies (Median) OS (Median, mos) PFS (Median, mos) ORR (%) CBR (%) Bria-IMT (Overall Cohort) 61 (38-81) 6 (2-13) 9.9 (1.8-30.3) 3.6 10% 55% Bria-IMT (Ph 3 Formulation) 62 (44-80) 6 (2-13) 13.43 (1.8-30.3) 3.6 (1.8-16.5) 14% 61% ASCENT (SG) 54 (27-82) 4 (2-17) 11.8 4.8 31% 40% ASCENT (TPC) 53 (27-81) 4 (2-14) 6.9 1.7 4% 8% TROPiCS-02 (SG) 57 (49-65) 3 14.4 5.5 21% 34% TROPiCS-02 (TPC) 55 (48-63) 3 11.2 4 14% 22% References: Bardia A et al. J Clin Oncol. 2024 May 20;42(15):1738-1744Rugo, Hope S et al. The Lancet, Volume 402, Issue 10411, 1423 – 1433.

Abstract Background: Bria-IMT™ is an allogeneic whole-cell cancer vaccine, designed to stimulate anti-tumor immunity (Chumsri et al 2024 ASCO). Bria-ABC (NCT06072612) is the multicenter, randomized, open-label trial evaluating overall survival (OS) of Bria-IMT™ regimen vs treatment of physician’s choice (PC) in patients with MBC where no meaningful therapy exists. Methods: 3 arm randomized 1:1:1 (Bria-IMT, Bria-IMT+CPI, or PC) in late stage heavily pretreated pts with MBC. Pts can be ECOG <2, Pts w/ CNS mets and/or who have received prior CPI or ADCs are allowed. The Bria-IMT™ regimen includes preconditioning w/ cyclophosphamide (300 mg/m2) on day -2/-3, intradermal SV-BR-1-GM inoculations (x4) on day 0, and interferon at inoculation sites (Days 1-3). CPI (retifanlimab 375 mg) may be given between days -2 to 2. The regimen is administered every 3 weeks (Q3W). Pts randomized to the monotherapy arm (Bria-IMT™ alone) may cross over to the combo arm upon disease progression. Response assessments are planned Q6W for the first cycle, and then Q8W thereafter. Based on prior data, an interim HR of 0.6 at 144 events will constitute early success. Overall study design anticipates 404 total pts. Results: This interim, unaudited data reflects ongoing enrollment and trial feasibility. To date, 61 pts have completed screening, with 40 pts randomized. Screened pts had a median age of 56 (range 35-82). For pts with evaluable data (n=40), median BMI was 25.6 kg/m2 (8.7-45.7) with a median of 6 (2-13) prior lines of therapy. 20 pts (50%) had HR+/HER2- breast cancer, 18 HR-/HER2- (45%), and 2 HER2+ (5%). Baseline ECOG PS were: 0 (55%), 1 (35%), 2 (10%). In biomarker-evaluable pts, circulating tumor cells were present at baseline in 30% (mean: 10.1 cells/mL; range: 0-139), while cancer-associated macrophage-like cells (CAMLs) were present in all pts (mean: 18.3 cells/mL; range: 1-154). In pts with available follow-up data, median change in CAML count from baseline to most recent cycle was -23.5%. In pts with available HLA typing, match distribution was 0 (19%), 1 (35%), 2 (26%), 3 (16%), and 4 (3%), 8 (26%) class 1, 8 (26%) class 2, and 9 (29%) matching both alleles informing potential immune response interactions with Bria-IMT™. Local injection site reaction (DTH), tumor-marker serum level, and circulating cancer cells, will be analyzed across subtypes to further characterize the pt population. The Bria-IMT™ regimen has been generally well tolerated, with no Tx D/C due to adverse events (AEs). The most frequently reported AEs include nausea (30%), constipation (22.5%), injection site rxn (22.5%), and headache (17.5%) w/ no interstitial lung disease reported. Discussion: Bria-ABC enrollment is ongoing. Future analyses will assess OS, PFS, ORR, CBR, QoL, and CNS event-free survival as data becomes available. Expected to close to enrollment by 2025, with final analyses planned for 2026. Citation Format: Saranya Chumsri, Joyce A. OShaughnessy, Azka Ali, Christopher N. Vaughn, Lawrence M. Negret, Adam Brufsky, Regina Stein, Marcela Salgado, Blaise Bayer, Giuseppe Del Priore, Sara A. Hurvitz. Bria-ABC vs physician choice in late stage MBC: Early biomarker correlates of the randomized registration trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB408.

Abstract Background: Bria-IMT™ is a combination immunotherapy consisting of allogeneic whole-cell cancer vaccine (SV-BR-1-GM) administered w/ immune checkpoint inhibitor (CPI). SV-BR-1-GM breast cancer cells have been engineered to directly stimulate anti-tumor immunity through expression of tumor-associated antigens and secretion of GM-CSF to enhance dendritic cell activation. Addition of CPI potentiates SV-BR-1-GM to overcome the immune-suppressive tumor microenvironment. Methods: This Phase I and randomized phase II combination study evaluated the Bria-IMT™ regimen: preconditioning w/ CTX (300 mg/m2) on day -2 or -3, SV-BR-1-GM inoculation and CPI administration on Day 0, and low-dose peg- interferon α at inoculation sites 2 (±1) day post-SV-BR-1-GM. Phase II pts were randomized 1:1 to receive CPI at cycle 1 (immediate) or cycle 2 (delayed). Two SV-BR-1-GM formulations (w/ and w/o IFNγ incubation) were evaluated. Biomarkers included cancer-associated macrophage-like cells (CAMLs), circulating tumor cells (CTCs), PD-L1 scores, and delayed-type hypersensitivity (DTH) skin tests. Results: 54 pts (22 in Phase I, 32 in Phase II) enrolled. 11 pts received pembrolizumab, 44 retifanlimab, w/ 1 pt transitioning from pembrolizumab to retifanlimab. Median age 61(38-81) years; median 6(2-13) prior regimens. 33(61%) pts were ER+/PR+/HER2-, 18(33%) TNBC, and 3(6%) HER2+. Bria-IMT regimen was well tolerated, w/ no attributable Tx D/C. 67% of adverse events grade 1-2; 13% ≥ grade 3 including pulmonary embolism, increased lipase, and dehydration. Median overall survival (OS) was 9.9 (1.8 - 30.3) mos w/ 13% of pts in active survival follow-up. Median progression free survival (PFS) was 3.2 (1.1-16.5) mos w/ 1 pt still in treatment (16.5 mos). Pts treated w/ ph 3 formulation (w/o IFNγ; N = 37) had significantly improved PFS (3.6 vs. 2.6 mos, P=0.01) and OS (13.4 vs. 6.9 mos, P=0.01); in evaluable pts, objective response rate was 14% and clinical benefit rate 61%. Randomized pts receiving ph 3 formulation had not reached median OS. In randomized pts, C1 vs C2 CPI initiation showed greater PFS (3.7 vs. 3.2 mos, P=0.09) and OS (11.4 vs. 7.4 mos, P=0.19). OS in pts w/ no HLA match was undefined vs 8.6 mos in pts w/ any match (P = 0.04). DTH (+) vs (-) correlated w/ greater OS (11.9 vs. 4.7 mos, P= <0.0001) and PFS (3.5 vs. 2.4 mos, P=0.001). Conclusion: Randomized phase 2 Bria-IMT demonstrated efficacy and safety in heavily pretreated MBC. Post-progression survival exceeding median OS in pts still undergoing survival follow-up suggests long-term benefit extending beyond treatment period. C1 vs C2 CPI initiation showed no statistical or clinically significant difference in OS. Superior outcomes w/ phase 3 formulation support its use in future trials. These results confirm earlier reports of the trial and an even greater benefit. A randomized phase 3 trial is ongoing comparing Bria-IMT vs treatment of physician's choice (NCT06072612). Trial Information: NCT03328026 Citation Format: Saranya Chumsri, Chaitali Nangia, Minal Barve, Kendrith Rowland, Ralph Boccia, John Knecht, Blaise Bayer, Marcela Salgado, Tamar Aghajanian, William V. Williams, Charles Wiseman, Giuseppe Del Priore, Carmen Calfa. Survival outcomes in a randomized phase 2 ofBria-IMT: An allogeneic whole cell cancer vaccine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT100.

1022 Background: The Bria-IMT regimen is a combination immunotherapy using an allogeneic whole cell cancer vaccine combined with checkpoint inhibitors (CPIs). Intradermally administered irradiated SV-BR-1-GM breast cancer cells secrete GM-CSF and present tumor associated antigens (TAAs) on HLA-I and –II molecules to directly stimulate anti-tumor immunity. Anti-PD1 CPI further stimulates T-cells and synergizes with SV-BR-1-GM. Here we report the results of the phase 1/2 trial (NCT03328026) of Bria-IMT in metastatic/advanced breast cancer evaluating sequencing of SV-BR-1-GM inoculation and CPI. Methods: Analysis of the phase 1 with expansion phase 2 cohort randomized by sequence using SV-BR-1-GM, checkpoint inhibitor (pembrolizumab or retifanlimab), low dose cyclophosphamide (Day –2) and post-dose local pegylated interferon α, with cycles every 3 weeks. In the 1:1 randomized cohort, CPI is either dosed at C1 prior to SV-BR-1-GM (original sequence) or delayed to C2 post-SV-BR-1-GM (alternative sequence). Cancer-associated macrophage-like cells (CAMLs) and circulating tumor cells (CTCs) were monitored as biomarkers. Results: A total of 54 patients were dosed: 11 with pembrolizumab, 44 with retifanlimab (1 patient received pembrolizumab and later retifanlimab). Median age=61 (38-81); Median prior regimen=6 (2-13); 72% ER+/PR+/HER2-; 6% HER2+ and 22% triple negative. Bria-IMT regimen was well tolerated with only 9% drop-out rate due to AE. AEs related to IPs were seen in 74% of patients; the majority (91%) being grade 1-2, and few (1.7%) grade 4 cases including pulmonary embolism, dehydration and increased lipase. Among 30 patients with post-dose CAML/CTC data and evaluable outcome, CAML count <5 associates with disease control (p=0.06, Chi square test). Patients who developed DTH to SV-BR-1-GM had significantly better PFS and higher OS. Patients treated with phase III formulation had an increase in PFS. Quality of life improvement correlates with disease outcome and survival. Among the patients treated with the phase III formulation of SV-BR-1-GM (n=23 with evaluable outcomes), objective response rate (ORR) is 13% and disease control rate (DCR) is 61%, with median PFS and OS are 4.1 and 13.3 months, respectively. In the randomized portion, the original sequence cohort had higher DCR (43% vs 36%) and OS (P=0.08, HR 0.30, 95%CI 0.08-1.17) compared to the alternative sequence cohort. Conclusions: BRIA-IMT has shown a favorable safety profile while providing benefits to heavily treated aMBC patients. Superior outcomes and survival were seen in patients treated with the phase III formulation and regimen now being used in the ongoing Ph3 trial, confirming the improvement in efficacy of the novel regimen. The results from this randomized phase 2 study informed the study design of the ongoing Ph3 trial comparing BRIA-IMT to standard of care physician choice treatments (NCT06072612). Clinical trial information: NCT03328026 .