Citations

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.

Objective: Multicancer Detection (MCD) tests, such as the GRAIL Galleri, offer a novel approach to cancer screening by detecting cancer-specific methylation patterns in cell-free DNA through a single blood sample. This study evaluated an 18-month implementation of MCD testing in a tertiary ambulatory internal medicine clinic. Patients and Methods: Between June 2022 and November 2023, 2244 asymptomatic (without symptoms attributed to cancer) patients underwent MCD testing. The study focused on operational workflows, patient and physician education, and diagnostic follow-up of positive results. Standardized materials, including electronic health record (EHR) workflows, FAQs, and diagnostic pathways, were developed to facilitate implementation. Challenges included managing false positives, patient anxiety, costs, and ethical considerations. Results: Of the 2244 patients tested, 17 (0.76%) had positive results, and 15 underwent further diagnostic evaluation. Cancer was confirmed in 11 (73.3%) patients, including cases of breast, colon, esophageal, lymphoma, ovarian, and pancreatic cancers. Four patients had no identifiable malignancy despite comprehensive work-up. Conclusions: MCD testing is feasible in routine clinical workflows, with 73% of positive cases yielding cancer diagnoses. While promising, further research is required to assess long-term outcomes, cost-effectiveness, and optimal implementation strategies of cancer interception in broader healthcare settings.

Background Novel treatment options are required in patients with platinum-resistant ovarian cancer (PROC). Myeloid-derived suppressor cells promote a hostile tumor microenvironment and are associated with worse clinical outcomes in PROC. We evaluated the safety and preliminary efficacy of PY159, an agonist antibody to Triggering receptor expressed on myeloid cells-1 (TREM1) that reprograms immunosuppressive intratumoral myeloid cells, and PY314, an antagonist antibody to Triggering receptor expressed on myeloid cells-2 (TREM2) that depletes tumor-associated macrophages, as single agents and in combination with pembrolizumab in subjects with PROC. Methods PY159 and PY314 were individually evaluated in patients with PROC. Patients were treated with monotherapy (PY159 3 mg/kg or PY314 10 mg/kg), based on the recommended dose for expansion derived from the phase 1a studies. At the time of first progression, patients could continue study drug and crossover to combination therapy with pembrolizumab (200 mg) every 3 weeks at the discretion of the investigator. Disease assessment by Response Evaluation Criteria in Solid Tumor version 1.1 was performed every 6 weeks. Results 17 patients were enrolled in the PY159 study (median age 67, range 22–77; median prior therapies 6, range 2–18) and 16 patients in PY314 (median age 65.5, range 49–81; median prior therapies 4, range 2–10). 7 patients in PY159 and 8 patients in PY314 crossed over to combination therapy. Safety events included the following: treatment-related adverse events occurred in 15 patients (88.2%) in PY159 and 9 patients (56.3%) in PY314. Infusion-related reactions occurred in 6 patients (35.3%) in PY159 and 3 patients (18.8%) in PY314. Immune-related adverse events occurred in 13 patients (76.5%) in PY159 (arthralgias) and 1 patient (6.3%) in PY314 (diarrhea). Serious adverse events occurred in 6 patients (36.3%) in PY159 (1 related) and 12 patients (75%) in PY314 (all unrelated). The best radiographic response in PY159 was stable disease in 8/16 patients (50%; median 16 weeks, range 9–33), and in PY314, it was stable disease in 8/16 patients (50%; median 12 weeks, range 6–36). Median PFS was 2.76 months and 2.69 months in PY159 and PY314, respectively. There were no responses in the crossover arm. Conclusions Both PY159 and PY314 were well tolerated, with an acceptable safety profile, as both single agents and in combination with pembrolizumab. Both agents warrant further investigation in heavily pretreated PROC.

Background Patients enrolling in hospice care are asked their preferences for antibiotic treatment. There is little information regarding which patients are more likely to receive antibiotics. To better inform discussions, we sought to characterize the use of antibiotics in the outpatient hospice setting. Methods We performed a retrospective review of patients enrolled in outpatient hospice within the Mayo Clinic Health System from 1/1/2017 through 1/1/2023. We calculated what percent of patients received antibiotics based on Hospice Qualifying Condition (HQC), age at enrollment, sex, survival time, and Charlson Comorbidity Index and calculated adjusted odds ratios (aOR). We documented which antibiotics were prescribed based on HQC. Results Of 6452 patients identified, 1259 (19.5%) received antibiotic prescriptions. Cephalosporins were the most common class of antibiotics prescribed (22.8% of antibiotics prescribed), followed by fluoroquinolones (20.3%) and penicillin derivatives (14.9%). Patients with Pulmonary HQCs were most likely to receive antibiotics (28.6% aOR 1.85 [1.51-2.25]), those with neurologic HQCs were least likely (14.9% aOR 0.66 [0.53-0.83]). There was no difference of age for those receiving antibiotics (80.7 yr) vs those not receiving (80.3 yr [ P = 0.25]), or for sex (male vs female aOR 1.10 [0.96-1.26). 4.6% of those surviving <7d received antibiotics (aOR .22 [0.17-0.29]), compared to 47.7% of those surviving >6mo (aOR 4.46 [3.50-5.69]). Discussion 19.5% of patients will receive antibiotics during their hospice course, with more frequent prescriptions in those surviving longer periods and those enrolled for pulmonary conditions. It is important to clarify patient preferences regarding antimicrobial utilization at the time of hospice enrollment.

Abstract Background At the time of hospice enrollment, patients are asked whether they would potentially want antibiotics. This is little information regarding which patients are more likely to receive these antibiotics or the impact on comfort or longevity. To help guide discussions with patients and families and target future stewardship interventions, we sought to characterize the use of antibiotics in the outpatient hospice setting. Methods We performed a retrospective review of patients enrolled in hospice with the Mayo Clinic Health System -Midwest from 1/1/2017 through 1/1/2023. For those with documented Hospice Qualifying Condition (HQC), we assessed age at enrollment, gender, survival time (ST), and Charleston Comorbidity Index (CCI). We documented which antibiotics were prescribed and compared the rate of prescription based on the above characteristics. Results We identified 6452 patients with identifiable HQC. Of these, 1281 patients (19.8%) received 4173 antibiotic prescriptions. After removing refilled prescriptions, there were 2037 new prescriptions. Cephalosporins were the most common class of antibiotics prescribed (24.4% of antibiotics prescribed), followed by fluoroquinolones (19.9%), penicillin derivatives (14.4%), and trimethoprim (10.4%) (fig 1). Pulmonary (28.6%) and GI (31.9%) HQCs were most likely to receive antibiotics, neurologic was least likely (fig 2). There was no difference of age for those receiving antibiotics (80.6 yr) vs those not receiving (80.3 yr [p=0.53]), or for gender (male vs female OR 0.97 [0.86-1.10). CCI was higher in those patients who received antibiotics (4.3) than those not receiving (3.93, p&lt; 0.001). Patients were more likely to receive antibiotics the longer they survived on hospice (4.7% surviving &lt; 7d, 47.7% surviving &gt;6mo – fig 3). Conclusion Antibiotics are an important pharmaceutical tool in the hospice setting. Nearly 20% of patients in hospice will receive antibiotics during their hospice course, with higher chance in those surviving longer periods and those enrolled for GI or pulmonary reasons. Discussions of antibiotic are crucial for these groups, and antimicrobial steward efforts should consider focusing on these patients. Disclosures All Authors: No reported disclosures

Abstract Background Minocycline is a second-generation tetracycline with a broad antimicrobial spectrum. It is often used in chronic suppression of musculoskeletal infections, given activity against gram positive organisms. Efficacy of Minocycline against gram negative skin and soft tissue infection has not previously been defined. In this study, we review in vitro minocycline efficacy against isolates from skin, muscle, and bone sources.Fig 1.Organisms isolated Methods We conducted a retrospective review of all minocycline susceptibility testing performed on musculoskeletal GNB isolates performed at the Mayo Clinic reference lab between 2013-2022. We describe the isolates broken down by site of culture and organism isolated. Then, we calculated the overall susceptibility of these isolates to Minocycline and susceptibility of the most common 6 organisms isolated.Fig 2.Sites of gram negative isolation Results During the study timeframe, we identified 13,567 gram negative isolates from musculoskeletal sites. Of 330 species identified, 19 were identified in at least 100 isolates (fig 1). Of 36 unique sites, 19 sites were each identified in at least 100 isolates (fig 2). 1920 isolates were tested for susceptibility to minocycline. Of these, 1584 (82.5%) were susceptible to minocycline. Of the most common organisms identified and tested for minocycline susceptibility, 99% of Stenotrophomonas maltophilia, 83% of Enterobacter cloacae, 80% of Escherichia coli, 68% of Acinetobacter baumanii, 1% of Proteus mirabilis, 53% of Klebsiella pneumoniae, 65% of Serratia marcescens isolates were susceptible to minocycline (fig 3). Pseudomonas aeruginosa isolates were not tested, due to innate resistance.Fig 3.Minocycline susceptibility compared to key organisms Conclusion A majority of skin and soft tissue cultures positive for Gram negative isolates were below the waist line. Of these, we reported organisms most commonly found. Minocycline showed in vitro activity against some commonly isolated gram negative organisms, especially E.coli, Acinetobacter, and Stenotrophomonas. Further research is needed into the efficacy of minocycline in gram negative skin and soft tissue infections, but it may represent a viable oral option, especially in the end of life. Disclosures All Authors: No reported disclosures

Abstract Background Staphylococcus lugdunensis (SL) is a coagulase-negative staphylococcus with virulence comparable to that of Staphylococcus aureus. The “skip phenomenon” (SP) is a pattern where blood cultures are intermittently negative before final clearance of bloodstream infection (BSI). SP is well-documented in S. aureus bacteremia but has not been described previously in SL. In this report, we present a cohort with SL BSI and describe its prevalence and their clinical features and outcomes. Methods We conducted a retrospective review of patients with blood cultures positive for SL in samples referred to the Mayo Clinic reference lab between June 2012 and June 2022. We assessed clinical characteristics, including time to positivity, prevalence of the skip phenomenon (defined by a positive culture after 24 hours of negative cultures), patient demographics including Charlson Comorbidity Index, mortality and length of hospital stay. Results We identified 55 patients with SL BSI and 33 of them had enough laboratory data to determine the prevalence of the skip phenomenon. SP was present in 5 of 33 (15.2%) patients. For all patients with SL BSI, the median age was 67 years (interquartile range [IQR] 61-79); mean CCI in the group with SP was 5.6 (standard deviation 2) and those without SP was 5.9 (standard deviation 2.7); median duration of bacteremia was 3 days (IQR 1-4); median hospital length of stay was 14 days (IQR 8-20); and 1-year mortality was 45%. Oxacillin susceptibility was present in 33 of 34 cases. Conclusion A total of 15% of patient cases with SL BSI demonstrated the SP. Recognition of the SP in patients with SL BSI is important as this may impact duration of antibiotic therapy and timing of long-term cardiovascular device placement. Disclosures Larry M. Baddour, MD, UpToDate, Inc.: Royalty payments (authorship duties).

131 Background: KRAS G12C mutations occur in 3%–4% of CRC cases and are associated with poor prognosis. In the phase 1/2 KRYSTAL-1 study (NCT03785249), at a median follow-up of 11.9 months (mo), Ada (irreversible inhibitor of KRAS G12C ) in combination with Cetux (anti-EGFR antibody) demonstrated promising clinical activity (objective response rate [ORR] of 34% per blinded independent central review [BICR] and 43% per investigator [INV]) and was well tolerated in patients (pts) with previously treated KRAS G12C -mutated mCRC. Based on these findings, Ada + Cetux was granted accelerated approval in the United States for these pts. Here, we present longer-term follow-up analyses from this study. Methods: Adults with previously treated KRAS G12C -mutated mCRC and ECOG performance status of 0 or 1 were treated with Ada (600 mg BID) in combination with Cetux (400 mg/m 2 followed by 250 mg/m 2 QW or 500 mg/m 2 Q2W) until disease progression, unacceptable toxicity, withdrawal of consent, or death, in separate phase 1 and phase 2 cohorts. Primary endpoints were safety (phase 1) and ORR per BICR (phase 2). Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (phase 2). Results: A total of 94 pts received Ada + Cetux. The median number of prior lines of systemic therapy was 3 (range, 1–9); 23 pts (24%) had received ≥ 4 prior lines of systemic therapy. The most frequent sites of metastases at baseline were the lung (71%) and liver (64%). At a median follow-up of 20.4 mo, ORR per INV was 43% (95% CI 32–53) and all were partial responses; median DOR was 5.9 (95% CI 5.5–7.6) mo. Disease control rate per INV was 86% (95% CI 78–92). Median PFS per INV was 6.9 (95% CI 5.9–7.4) mo; 6- and 12-mo PFS rates were 61% and 19%, respectively. Median OS was 16.0 (95% CI 13.3–18.8) mo; 6- and 12-mo OS rates were 88% and 66%, respectively. Any-grade treatment-related adverse events (TRAEs) were reported in 100% of pts, 28% of which were grade 3/4. TRAEs led to discontinuation in 10% of pts. Efficacy analyses by BICR, subgroup analyses, and additional safety results will be presented. Conclusions: In heavily pretreated pts with KRAS G12C -mutated mCRC, Ada + Cetux continued to demonstrate clinically meaningful activity and tolerable safety with longer follow-up. These updated results are consistent with those from the primary analysis and constitute the longest duration of follow-up for dual KRAS G12C /EGFR blockade in this setting. Efficacy of second-line Ada + Cetux vs chemotherapy in KRAS G12C -mutated mCRC is being investigated in the phase 3 KRYSTAL-10 study (NCT04793958). Clinical trial information: NCT03785249 .

Abstract Background Progress in clinical trials and drug development for paediatric perianal fistulising CD (pfCD) depends upon accurate, reproducible imaging to assess disease activity and measure treatment response. We evaluated the inter- and intra-rater reliability of existing radiologic disease activity indices and anatomical classification systems previously identified as appropriate for assessment of paediatric pfCD.1 Methods A retrospective cohort (N=50) of magnetic resonance imaging (MRI) exams representing a full spectrum of paediatric (&lt;18 years) perianal CD severity was selected by a single expert paediatric radiologist. Methods described by Zou2 were used to estimate sample size. Three separate radiologists (2 paediatric) blinded to clinical information assessed pfCD in the exams using the Magnetic Resonance Novel Index for Fistula Imaging in CD (MAGNIFI-CD), Van Assche Index (VAI), modified VAI (mVAI), Paediatric MRI based Perianal Crohn’s disease (PEMPAC) index, a visual analogue scale (VAS) of overall pfCD disease severity (range, 0-100 mm), as well as with the Park’s and St. James University Hospital anatomic classification systems. Two radiologists read all exams twice, separated by 2 weeks, and 1 radiologist read the exams once (250 total reads). Intra- and inter-rater reliability was evaluated using intraclass correlation coefficients (ICC; equivalent to weighted kappa). Precision of the ICC estimates was quantified with 95% confidence intervals (CIs) obtained using clustered bootstrapping. Degree of reliability was interpreted with benchmarks proposed by Landis and Koch3. Results Median age of children was 13.5 years (IQR 11.4-16.1), and 64% were male. Median Paediatric Crohn’s Disease Activity Index score at time of imaging was 17.5 (IQR 10-32.5). Substantial (ICC&gt;0.61) inter-rater reliability was observed for MAGNIFI-CD, VAI, and mVAI (Table 1), with the highest ICCs observed for the mVAI (0.72 [0.6 to 0.79]). Moderate (ICC&gt;0.41) inter-rater reliability was observed for PEMPAC, St. James University Hospital classification, and the VAS, and fair (ICC&gt;0.21) inter-rater reliability was observed for Parks classification. Intra-rater reliability was nearly perfect (ICC&gt;0.81) for the VAS, and substantial for all indices except for Parks classification, which had moderate (0.60 [0.44 to 0.75]) intra-rater reliability (Table 1). Conclusion Most existing multi-item MRI-based disease activity indices and the St. James Hospital classification were reliable for the assessment of paediatric pfCD in our cohort. Our preliminary results suggest that the disease activity indices may have utility to measure treatment effect in paediatric pfCD clinical trials. References 1.Crowley E, Ma C, Guizzetti L, Zou G, Lewindon PJ, Gee MS, et al. Recommendations for Standardizing MRI-based Evaluation of Perianal Fistulizing Disease Activity in Pediatric Crohn's Disease Clinical Trials. Inflamm Bowel Dis. 2024;30(3):357-69. 2.Zou GY. Sample size formulas for estimating intraclass correlation coefficients with precision and assurance. Statistics in Medicine. 2012;31(29):3972-398 3.Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33(1):159-74.

Abstract The skip phenomenon (SP) is a pattern where blood cultures are intermittently positive before final clearance. We report that one-third of patients with Staphylococcus lugdunensis infective endocarditis experienced the SP. Patients with the SP experienced both a longer duration of bacteremia and hospital stay, with a higher 1-year mortality rate.