Ali, Azka

Abstract Background S0221 investigated weekly vs every 2 weeks dosing of doxorubicin (A) and cyclophosphamide (C) followed by paclitaxel in patients with high-risk early breast cancer. After an interim analysis, random assignment to the 2 AC arms was stopped for futility, and the trial was modified to study only the paclitaxel schedules. Methods Between December 2003 and November 2010, a total of 2716 patients were randomly assigned in a 2 × 2 factorial design to 15 weeks of weekly A and daily C vs 6 cycles of every 2 weeks AC; and weekly paclitaxel for 12 weeks vs 6 cycles of every 2 weeks paclitaxel. Between January 2011 and January 2012, an additional 578 patients were assigned to 4 cycles of every 2 weeks AC and randomly assigned to weekly vs every 2 weeks paclitaxel. Updated survival was assessed using log-rank tests and Cox regression models. We compared outcomes by breast cancer subtype as well. Results At a median follow-up of 12.1 years, there were no statistically significant differences among the 4 treatment arms in disease-free survival (DFS) (P = .91) or overall survival (P = .34) in the original protocol. Among the 578 patients assigned AC for 4 cycles and randomly assigned to paclitaxel weekly vs every 2 weeks paclitaxel, there were no overall differences in DFS (P = .32) or overall survival (P = .42). Conclusion As there were no statistically significant outcome differences in DFS or overall survival between the studied schedules of AC and paclitaxel with extended follow-up in the original or revised protocol, either paclitaxel schedule may be recommended, with selection based on toxicity, cost, or patient preference.

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 .

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.

TPS1122 Background: Treatment options for patients (pts) with unresectable or metastatic BC have improved with the development of novel targeted therapies including trastuzumab deruxtecan (T-DXd), an ADC directed against HER2 with a cytotoxic topoisomerase I inhibitor as a payload. Currently, there are limited treatment options for pts with HER2+ or HER2-low metastatic BC that has progressed on T-DXd. BB-1701 is an ADC consisting of a monoclonal antibody targeting HER2 with eribulin (microtubule inhibitor) as a payload that is capable of exerting a bystander effect. A first-in-human dose-finding Study 101 of BB-1701 is ongoing. Here we describe Study 205, an open label, multicenter, phase 2 study of BB-1701 in pts with HER2+ or HER2-low unresectable or metastatic BC who have disease progression after treatment with T-DXd. Methods: Study 205 (NCT06188559) includes dose-optimization and dose-expansion parts for BB-1701. Eligible pts must have histologically confirmed HER2+ or HER2-low, unresectable or metastatic BC, with measurable disease per RECIST v1.1. Prior treatment must include 1–3 prior chemotherapy-based regimens for unresectable or metastatic BC, including T-DXd. The primary objectives of the dose-optimization part include determining the recommended dose (RD) and evaluating safety and tolerability of BB-1701. The RD will be assessed by randomly assigning ~50 pts into 1 of 3 dosing cohorts (1.6 mg/kg on day 1 Q3W, 0.8 mg/kg on days 1 and 8 Q3W, and 1.2 mg/kg on day 1 Q3W; IV) in a 2:2:1 ratio. Randomization will be stratified by HER2 status (HER2+ vs. HER2-low) documented prior to T-DXd treatment. The dose-expansion part will enroll ~85 pts at RD; the primary objective includes evaluating the efficacy of BB-1701 at the RD. In both study parts, secondary objectives include assessment of additional efficacy measures (i.e., duration of response [DOR], progression free survival [PFS], overall survival [OS], disease control rate [DCR], clinical benefit rate [CBR], and time to response [TTR]), and pharmacokinetics. Efficacy endpoints will be assessed per RECIST v1.1 by the investigator during the dose-optimization part or by Blinded Independent Central Review during the dose-expansion part. Safety assessments will consist of recording, monitoring, and grading of adverse events (AEs) based on CTCAE v5.0, AEs of special interest, and serious AEs. In both study parts, exploratory objectives will include evaluation of biomarkers of response to BB-1701 and BB-1701 immunogenicity; other efficacy measures (i.e., PFS on the next line of therapy) and population pharmacokinetics will be analyzed in the dose-expansion part only. Pt enrollment is currently open. Clinical trial information: NCT06188559 .