Citations

e23011 Background: Eligibility criteria for clinical trials are crucial for maintaining safety and study integrity. However, they often exclude patients due to medical conditions that are not relevant, leading to gaps in understanding the real-world effectiveness of treatments. Addressing potentially modifiable exclusions (PMEs) could enhance accessibility and participation in trials without compromising safety, particularly given the low rates of enrollment. Methods: We retrospectively analyzed ‘screen-failed’ patients (those who were excluded after providing consent because they did not meet the eligibility criteria or other protocol requirements) with biliary tract (BTC) or pancreatic cancer (PDAC) between August 2019 and November 2024. Screening logs and electronic health records provided clinical data. PMEs were identified and validated by two independent medical oncologists. Results: Of 585 screen-failed patients from 18 trials, 76 were excluded due to incomplete data. Among the 509 patients analyzed (367-PDAC, 142-BTC), the leading causes of screen failure were declined participation (99, 19%), comorbidities (59, 12%), suboptimal organ function (56, 11%), absence of biomarker (49, 10%), and insufficient biospecimens (36, 7%). Among patients declining participation, reasons included preference for standard care (23%), travel (22%), competing trials (5%), adverse event concerns (4%), financial issues (3%), and unknown reasons (43%). Of the 509 patients deemed ineligible for study entry at screening, we identified 69 patients (13.6%) with PMEs, primarily related to borderline laboratory abnormalities: liver function (16, 23%), kidney function (14, 20%), platelet count (8, 12%), hemoglobin (5, 7%), and white blood cell count (4, 6%). Other PMEs included previous or concurrent malignancies (6, 9%) and viral hepatitis (3, 4%). PMEs were evenly distributed across trials. Notably, all screen-failed patients proceeded to receive standard therapy. Conclusions: This analysis underscores the potential for rigid eligibility criteria to exclude stable patients who might benefit from investigational treatments. Easing specific criteria, particularly those related to laboratory abnormalities, could broaden trial accessibility. Furthermore, examining the reasons for declined participation and addressing PMEs could help develop strategies to enhance trial enrollment.

5108 Background: We previously proposed a hybrid framework combining LLMs and rule based algorithm (RBA) for automating risk stratification in locPCa. Herein, we aim to validate the risk stratification agent (RSA) in a prospective cohort, develop & evaluate the treatment recommendation agent (TRA) based on NCCN guidelines, and develop an interactive interface to facilitate clinicians for accurate risk stratification and treatment recommendations at the point of care. Methods: This study included pts with locPCa (2004-2024) presenting at Mayo Clinic with at least 1 positive prostate biopsy and MRI report available. For RSA prospective validation, GPT4 extracted key phenotypic variables (PSA, T stage, prostate volume, number of cores, Gleason patterns, grade group) from unstructured MRI and biopsy reports using a zeroshot prompt. An RBA then classified pts into NCCN risk groups. The agent performance was compared with the treating clinician's documentation and evaluated against gold-standard labels manually annotated by two independent clinicians. For development of TRA, two experiments were performed using GPT4 with and without retrieval-augmented generation (RAG) to generate treatment plans. Generated treatment plans were evaluated using NCCN guideline-informed treatment decision tree based algorithm (DTA). Evaluation metrics, weighted – accuracy (acc) and F1, were computed. A clinician facing interface (lisr.org/risk) was developed to provide accurate risk stratification and treatment plans. Results: A total of 858 pts were included (500 for prospective validation, 358 for treatment recommendations). Prospective validation for RSA demonstrated a higher F1 score of 0.89 compared to the treating clinician (F1: 0.58). Treatment recommendation experiments showed that GPT4 with RAG achieved higher acc (64% full – all correct treatment options and 36% partial – at least 1 correct treatment option) compared to GPT4 alone (35% and 65%, respectively). Sensitivity analysis using DTA-informed GPT4 note generation achieved 94% full acc and 6% partial acc. GPT4 alone generated hallucinated treatment options in 71% of cases, while GPT4 with RAG reduced this to 32%. Conclusions: The multi-agent framework based on LLM and RBA achieves high accuracy in risk stratification and treatment recommendation for locPCa. A multi-agent framework with an interactive interface holds high promise to enable efficient, accurate decision-making, and improve locPCa management at the point of care Performance evaluation. RSA(acc; F1) % TRA(full acc; partial acc) % Clinician RSA* GPT4 RAG+GPT4 DTA+GPT4 Overall 60; 58 89; 89 29; 71 64; 36 94; 6 V. High 94; 33 96; 96 55; 45 69; 31 93; 7 High 46; 52 92; 89 - - - Int. Unf 80; 61 91; 90 5; 95 38; 62 93; 7 Int. Fav 57; 64 84; 87 0; 100 98; 2 100; 0 Low 57; 65 87; 80 100; 0 95; 5 90; 10 V. Low 8; 13 50; 67^ - - - *Statistical significance (p<0.01) except for ^V. Low.

1652 Background: Tarlatamab is a bispecific T-cell engager targeting DLL3 that has shown promise as a therapy in small cell lung cancer. Administering tarlatamab requires careful consideration of immune-related adverse events (AE), including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Prescribing information recommends patients to be monitored for 22-24 hours in an appropriate healthcare setting for cycle 1 (C1), days 1 and 8. At Mayo Clinic in Rochester MN (MCR), tarlatamab is initially administered in a hospital-based outpatient (HBO) setting utilizing an innovative remote patient monitoring system (RPM). In this study, we describe our RPM process and patient outcomes thus far. Methods: We retrospectively reviewed records of patients treated with tarlatamab from August through December 2024. All patients received tarlatamab in the HBO setting and were enrolled into RPM for C1, days 1–10. Patients attended daily HBO visits on days 1–3 and 8–10 of C1 and were required to stay within 30 minutes of the hospital with a 24-hour caregiver for 48 hours following infusion days in C1-2. Data on patient characteristics, frequency of RPM alerts, escalations, rate of CRS & ICANS, and need for hospitalizations were reported using descriptive metrics. Results: As part of RPM, patients are provided with a kit containing preconnected Bluetooth-enabled devices to measure vital signs (VS), including blood pressure (BP), heart rate (HR), temperature (T), and pulse oximetry (SpO2). The kit also includes a cellular-enabled tablet for electronic ICANS questionnaires, which upload directly into our electronic medical record system. Patients are required to log VS four times daily, monitored in real-time by a centralized virtual RPM nursing (RN) team. Embedded decision trees trigger alerts, prompting the RN team to contact patients and follow care pathways for escalations as needed. Among the 16 patients treated, the median age was 68 years, and the median ECOG PS was 1. During the 10-day RPM period, a total of 2,233 VS entries were recorded. Of these, 88% (14/16) of patients had alerts triggered, with a median of 2 alerts per patient. Alerts were mostly for out-of-range systolic BP (56%), HR (56%), and T (25%), with none for SpO2. The RN team escalated alerts in 50% (8/16) of the patients. Overall, 38% (6/16) of patients were managed entirely in the HBO setting. Among the 63% hospitalized, 56% had CRS limited to grade (G) 2, and 31% had ICANS limited to G3. Two patients were hospitalized for other indications. The mean length of stay was 2.6 days, with no ICU admissions. Conclusions: Our experience shows that frequent monitoring required with tarlatamab can be safely and effectively executed in an outpatient setting with the utilization of an RPM system. It can potentially minimize the burden of hospitalizations for patients and the healthcare system.

1649 Background: Findings from our prior large-scale comparative effectiveness trial showed the equivalent effect of delivering early palliative care via video versus in-person on quality of life among patients with advanced non-small cell lung cancer (NSCLC). We now report on whether the two care delivery modalities were equivalent with respect to patient-reported communication with clinicians about their end-of-life (EOL) care preferences and hospice utilization. Methods: Between 6/14/2018 and 5/4/2023, we enrolled 1250 patients with newly diagnosed advanced NSCLC in a randomized trial of early palliative care across 22 US cancer centers. Patients were randomly assigned to meet with a palliative care clinician every 4 weeks from enrollment through the course of the disease, either via video or in the outpatient clinic. Participants completed self-report surveys at baseline and weeks 12, 24, 36, and 48, including an item asking if they had discussed with their clinicians the care they would want to receive if dying (yes/no); patients’ final assessments prior to death or last follow up were analyzed. We reviewed patients’ health records to collect data on hospice referral and length of stay. To test the equivalence in these outcomes, we used a binomial generalized linear model with the identity link function (pre-specified equivalence margin of ±8% for patient-reported communication about EOL care) and linear regression (pre-specified equivalence margin of ±6 days for mean length of stay in hospice). P-values were adjusted for multiplicity using a Bonferroni correction. Results: Of the 1250 enrolled participants, 888 (71.0%) completed at least one survey post baseline regarding whether they communicated with clinicians about EOL care preferences. Among those, 29.1% of the video group and 26.0% of the in-person group reported “yes,” indicating that they recalled such EOL care discussions (difference = 3.1%, 95% CI: -1.8%, 8.1%; p = 0.26 for equivalence). During the course of the trial, 733/1250 (58.6%) patients died, of whom 537/733 (73.3%) were referred to hospice. Mean lengths of hospice stay were 25.3 days for the video group versus 25.1 days for the in-person group (difference = 0.2, 95% CI: -7.0, 7.4; p = 0.46 for equivalence). When excluding outlying patients receiving hospice services > 180 days (n = 13), the mean lengths of hospice stay were 19.1 (video group) versus 19.7 (in-person group) days (difference = -0.6, 95% CI: -4.6, 3.3; p = 0.06 for equivalence). Conclusions: Although thresholds were not met to confirm equivalence statistically, the two modalities for delivering early palliative care demonstrate very similar outcomes with respect to patient-clinician communication about EOL care and hospice utilization. These findings provide further evidence of the utility of video visits for providing high quality palliative and EOL care. Clinical trial information: ClinicalTrials.gov Identifier ( NCT03375489 ) .

Abstract Infection is increasingly recognized as a significant cause of morbidity and mortality in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) receiving CD19 chimeric antigen receptor (CAR) T-cell therapy. The current study analyzed the natural history, risk factors, and outcomes of infection in 3350 patients with R/R LBCL receiving commercial CD19 CAR T-cell therapy (n = 2804 axicabtagene ciloleucel [axi-cel], n = 546 tisagenlecleucel) from December 2017 to June 2022. Infection developed in 834 patients (24.9%) within 100 days after infusion, resulting in an infection density of 0.43 per 100 patient days and a 100-day cumulative incidence of 22%. Bacterial, viral, and fungal infections were recorded in 527 (15.7%), 374 (11.2%), and 108 patients (3.2%), respectively, with corresponding infection densities of 0.23, 0.15, and 0.04 per 100 patient days. After a 24-month median follow-up, 1482 patients (44%) had died, with infection as the primary cause in 173 cases (12%). The 100-day infection-related mortality (IRM) was 1.6% (95% confidence interval, 1.2-2.0). Patients with a Karnofsky performance score of ≤80, infection history before CAR T-cell therapy, axi-cel therapy, severe cytokine release syndrome (grade ≥3), and severe immune effector cell–associated neurotoxicity syndrome (grade ≥3) had increased infection risk. Infections within 100 days were an independent risk factor for inferior overall survival beyond day 100 after CD19 CAR T-cell therapy. In conclusion, study results show a significant incidence of infection and IRM in patients with R/R LBCL treated with CD19 CAR T-cell therapy. Furthermore, results identify patients at a heightened risk of infection, offering insights to guide potential interventions aimed at mitigating infection and improving patient outcomes after CAR T-cell therapy.

6106 Background: Treatment options for pts with R/M SGC are limited. Responses to chemotherapy (CT) are low with high toxicity and responses to immune checkpoint inhibition (ICI) are <10%. Pemetrexed (PTX) is safe and tolerable with responses reported in pts with R/M SGC. 1 Given enhanced responses with PTX and pembrolizumab (PMB) for lung cancer, we hypothesized that PTX and PMB will have activity for SGC. Herein we present the efficacy results in pts with non-adenoid cystic carcinoma (ACC). Methods: MC200708 is a single arm phase II study of PTX and PMB in pts with R/M SGC (NCT04895735). Pts were treated in 2 cohorts: ACC (cohort A) and non-ACC (cohort B). Key eligibility criteria: ≥18 years, ECOG 0-1, measurable disease. Prior ICI and/or PTX was allowed. Key exclusion criteria: serious comorbidities, autoimmune disease, and brain metastases. Simon’s 2-stage design was used for each cohort. Primary endpoint was overall response rate (ORR). Secondary endpoints: progression free survival (PFS), overall survival (OS), and toxicity. All pts received PTX 500 mg/m2 IV + PMB 200 mg IV q3 weeks until progression or treatment intolerance. Imaging was q3 cycles. Results: 25 pts were enrolled Aug 2021-Feb 2024; 1 cancelled prior to treatment. Of 24 eligible and treated pts, median age was 59.5 years (46-77), 66.7% male, performance status 0 (62.5%) or 1 (37.5%). Histologies were salivary duct carcinoma (SDC, 11), acinic cell carcinoma (8), mucoepidermoid carcinoma (MEC, 3), myoepithelial carcinoma (1), and carcinoma NOS (1). 7 pts had no prior therapies (29.2%). The remaining pts had 1 (33.3%), 2 (29.2%), or ≥ 3 lines of therapy (8.3%). 83.3% of pts had no prior ICI. Median cycles of treatment was 8 (2-34), and duration of response was 12.5 months (4.1-20.6). 9 of 24 pts had a confirmed partial response (PR) for ORR of 37.5% (CI: 18.8-59.4). PRs were seen in 7 pts with SDC (7 of 11, 63.6% PR), 1 with MEC, and 1 with acinic cell. Stable disease (SD) was seen in 5 (20.8%), progressive disease in 8 (33.3%), and 2 didn’t have post-baseline imaging, but were considered non-responders per protocol. Clinical benefit rate was 58.3% (CI: 36.6-77.9). With median follow-up of 12.0 months (2-34.7), median OS is 20.7 months (CI: 17.3-not reached) and median PFS is 6.2 months (CI: 2.1-17.3). 1-year OS and PFS rate is 76.3% (95% CI: 59.9-97.2) and 36.1% (CI: 21.01-62.2), respectively. Common toxicities were grade 1 fatigue and nausea. 6 pts (25.0%) had ≥1 grade 3-4 toxicity possibly related to treatment, mostly hematologic. The 4 pts with grade 3-4 non-heme toxicity had grade 3 fatigue, rash, and heart failure, and 1 grade 4 hypokalemia. Correlative studies investigating biomarkers of response are underway. Conclusions: PTX and PMB has activity in pts with R/M SGC, with promising responses in pts with SDC and median response duration of 1 year. 1 Viscuse et al. Head Neck 2019;41(6):E99-103. Clinical trial information: NCT04895735 .

ABSTRACTBackgroundIn this study, we compared outcomes of intensified myeloablative conditioning regimens using large registry data from Japan (Japanese Society for Transplantation and Cellular Therapy) and the United States (Center for International Blood and Marrow Transplant Research).MethodsAdult patients who underwent their first myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia in remission between 2010 and 2018 using conditioning regimens of cyclophosphamide plus total‐body irradiation (CY/TBI), CY/TBI+cytarabine (AraC), or CY/TBI+etoposide (VP16) were included.ResultsThe acute myeloid leukemia (AML) cohort (N = 480, 38.8%) indicated that overall survival (OS) was poorer in CY/TBI+AraC (hazard ratio [HR] 1.46, p < 0.001) and CY/TBI+VP16 (HR 1.39, p = 0.059) compared to CY/TBI. Relapse was not suppressed, while treatment‐related mortality (TRM) was significantly higher (HR 1.78 and 1.74, p < 0.001 and 0.018, respectively). In the acute lymphoblastic leukemia (ALL) cohort (N = 3901, 61.2%), OS was comparable among these regimens. With intensified regimens, relapse was significantly suppressed in CY/TBI+VP16 (HR 0.74, p = 0.005), while TRM was higher (HR 1.21, p = 0.077). No interactions were observed regarding the country.ConclusionIn AML adding AraC and VP16 to CY/TBI had an adverse effect on OS. Conversely, in ALL, adding VP16 or AraC to CY/TBI did not affect survival, but the addition of VP16 reduced the risk of relapse.Clinical Trial RegistrationThe authors have confirmed clinical trial registration is not needed for this submission.

e19538 Background: Patients with multiple myeloma (MM) and type 2 diabetes mellitus (T2DM) experience increased risks of morbidity and mortality. GLP-1 receptor agonists (GLP-1 RA) offer glycemic and cardiovascular benefits, but their impact on cancer-related outcomes is unclear. This study evaluates the association of GLP-1 RA therapy with clinical outcomes, MM-related biomarkers, and survival in MM patients with T2DM. Methods: We conducted a retrospective cohort analysis using the TriNetX network, including data from 104 healthcare organizations (2014–2019). Two cohorts were defined: (1) MM patients with T2DM starting GLP-1 RA therapy within three months of MM diagnosis and continuing therapy for at least one year (n=1,606 before matching), and (2) MM patients with T2DM not receiving GLP-1 RAs (n=40,306 before matching). Patients included were aged 18 years and older. One-to-one propensity score matching (PSM) balanced systemic MM therapy, BMI, and diabetes medications (e.g., insulin, metformin), yielding 1,279 matched pairs. Outcomes included five-year mortality, ICU and non-ICU hospitalizations, and MM-related biomarkers (hemoglobin, creatinine, neutrophils, and calcium). Most recent lab values were compared in the two groups. Statistical analyses included Kaplan-Meier survival estimates, hazard ratios (HR), risk differences, and T-Test statistics. Results: After PSM, baseline characteristics were well balanced. The mean age was ~ 66 years, white race was ~46%, females were ~ 40%, and hypertension was ~85%. Around 20% of MM patients received autologous transplants and ~27% received lenalidomide in the past. GLP-1 RA therapy was associated with less mortality (HR: 0.44, 95% CI: 0.36–0.54, P < 0.01), ICU admissions (HR: 0.59, 95% CI: 0.50–0.71, P < 0.01), and non-ICU hospitalizations (HR: 0.59, 95% CI: 0.53–0.65, P < 0.01). Patients on GLP-1 RAs had higher hemoglobin levels (11.61 ± 2.30 g/dL vs. 10.75 ± 2.47 g/dL, P < 0.01), with no significant differences in serum creatinine (119.068 µmol/L vs 115.648 µmol/L, P = 0.720) or neutrophils (P = 0.226). Patients who received GLP-1 RAs had higher serum calcium levels (9.17 mg/dL vs. 8.96 mg/dL, P < 0.01). GLP-1 RA use also decreased the incidence of septic shock (HR: 0.53, 95% CI: 0.44–0.64, P < 0.001) and pneumonia (HR: 0.59, 95% CI: 0.49–0.70, P < 0.001). Conclusions: GLP-1 RA therapy improves survival, reduces ICU and non-ICU hospitalizations, and lowers complications in MM patients with T2DM. Biomarker trends over five years suggest potential anticancer effects. Further research should explore whether GLP-1 RAs impact other malignancies, broadening their role in cancer therapy.

11506 Background: Catequentinib Hydrochloride (AL3818, Anlotinib, Catequentinib) is a novel, orally administered, small molecule tyrosine kinase inhibitor. There remains an unmet need for effective, well tolerated therapies for patients (pts) with advanced/ metastatic leiomyosarcoma (LMS). We performed a randomized, double blind trial of Catequentinib monotherapy versus placebo in advanced/metastatic LMS. Methods: Patients with a diagnosis of LMS requiring third or further line treatment were eligible. Catequentinib was administered in a 21-day cycle with 14 days on and 7 days off regimen. In this double blind phase 3 trial, patients were randomized 2:1 to Catequentinib or placebo, with the option of crossover to Catequentinib after confirmed Progression Disease (PD) on placebo. Progression-free survival (PFS) with Log Rank test was the primary endpoint and the trial was conducted at multiple sites in the US, UK and EU. Results: Total N = 111 patients were enrolled, and N = 110 were treated and evaluated, 74 randomized to Catequentinib (C), and 36 to placebo (P). In arms (C)/(P) median ages were 59.0/60.5 (range: 33-91) years respectively and 59/29 (79.7%/80.6%) were female. Median PFS by Blinded Independent Central Review (BICR) met the primary endpoint at 3.42 months (95% CI: 2.60, 6.83) for (C) and 1.41 months (95% CI: 1.35, 4.86) for (P) with a p-value of 0.0265 and a HR of 0.536 (95% CI: 0.307, 0.936). Median PFS for patients stratified at ≤ 3 prior lines was 4.86 months (95% CI: 2.04, 8.94) for (C) and 1.41 months (95% CI: 1.31, 4.86) for (P) with a p-value of 0.0046 and a HR of 0.386 (95% CI: 0.196, 0.760). The 6-month progression-free rate was 42.37% for (C) and 20.71% for (P). OS was 17.45 months (95% CI: 13.57, 19.32) for (C) and 16.33 months (95% CI: 11.27, NE) for crossover patients in the (P) arm. 30 (40.5%) of patients have experienced grade 3 treatment-related adverse events in the (C) arm compared to 3 (8.3%) of patients in the (P) arm. The most common TEAE for (C) vs (P) were diarrhea (50.0% vs 22.2%), stomatitis (31.1% vs 8.3%), fatigue (64.9% vs 41.7%), and hypertension (47.3% vs 19.4%). Conclusions: This phase 3 trial met the primary PFS endpoint and demonstrates superior PFS for Catequentinib vs placebo in metastatic/advanced LMS. This study confirms the acceptable benefit-risk profile of Catequentinib in LMS. Catequentinib is an effective and well tolerated treatment option for patients with LMS. Clinical trial information: NCT03016819 .

TPS1125 Background: Despite the many available treatments for patients (pts) with HR+, HER2– recurrent/metastatic breast cancer (MBC), optimal treatment after progression on CDK4/6 inhibitors (CDK4/6i) is unclear. One possible CDK4/6i resistance mechanism is increased expression of Aurora kinase A (AURKA), a key mitosis regulator associated with poor prognosis. Further implicated in CDK 4/6i resistance, high c-Myc or RB1 loss of function (LOF) are associated with transcriptional co-regulation or synthetic lethality, respectively, with AURKA. Alisertib is a highly selective, reversible, ATP-competitive, orally administered, small-molecule AURKA inhibitor with antiproliferative activity in HR+ BC-derived cell lines and BC xenograft models. Models with elevated AURKA or c-Myc expression, or RB1 LOF show greater alisertib sensitivity. Alisertib had activity in phase 1 and 2 trials, including objective response rates (ORRs) of 19.6–20% and median progression-free survival (PFS) of 5.4–5.6 months alone or with fulvestrant in pts with HR+/HER2–, endocrine-resistant MBC. The most common treatment-related grade ≥3 adverse events (AEs) were neutropenia, anemia, and leukopenia. Methods: ALISCA-Breast1 (NCT06369285) is a randomized phase 2 study. Primary objective: to determine the optimal alisertib dose administered with endocrine therapy (ET) based on AEs and serious AEs per CTCAE v5.0 and efficacy (ORR, duration of response, disease-control rate, PFS, overall survival). Secondary objectives: to identify biomarkers of efficacy and alisertib pharmacokinetics (PK). Key inclusion criteria: ≥18 years; ECOG performance status 0 or 1; confirmed HR+, HER2–, recurrent/metastatic breast adenocarcinoma not amenable to curative therapy; available tumor tissue for biomarker analyses; progression on or after ≥2 prior ET lines in recurrent/metastatic setting; prior CDK4/6i with ET in recurrent/metastatic setting. Key exclusion criteria: prior chemotherapy in recurrent/metastatic setting; prior AURKA-specific or pan-Aurora-targeted agents; unstable brain metastases. Eligible pts will be randomized 1:1:1 to alisertib 30 mg, 40 mg, or 50 mg orally twice daily on days 1−3, 8–10, and 15–17 every 28 days, plus physician’s choice of anastrozole, letrozole, exemestane, fulvestrant, or tamoxifen not previously used in recurrent/metastatic setting or progressed upon in adjuvant setting; ≤50 pts will be enrolled per arm in the USA and Europe. All pts will undergo sparse PK sampling. Tumor tissue will be centrally assessed for biomarkers, including RB1, MYC, TP53, ESR1, PI3K/AKT pathway, HER2 and AURKA genomic alterations/expression levels. The study will determine the optimal alisertib dose to combine with ET and may identify biomarker(s) defining pts with the greatest benefit from alisertib-based therapy. Clinical trial information: NCT06369285 .