Steinert, Kimberly O.

678 Background: Financial toxicity (FT) represents a challenge for cancer patients that impacts treatment decisions, patient satisfaction, and quality of life. Social determinants of health (SDoH) screening may predict who is at risk of FT and could potentially benefit from financial interventions. Methods: This is a retrospective study of all cancer patients presenting to Mayo Clinic sites between Sept 2023 – Jun 2024. Patients completed SDoH questionnaires and were given risk scores of Low Risk, Medium Risk, and High Risk for SDoH categories: Financial Strain Risk, Transportation Risk, and Food Insecurity Risk. Patient financial data including active debt amounts, insurance coverage, and financial aid were collected. Patients with pancreatic ductal adenocarcinoma (PDAC) were compared to those with pancreatic neuroendocrine tumors (PNET) and patients with other cancers (Others). Categorical variables were compared with Pearson's Chi-squared test, continuous variables with Kruskal-Wallis rank sum test. P values < 0.05 were considered significant. Results: Data was obtained from 88,039 patients, 2,607 of whom had PDAC and 449 had PNET. Compared to PDAC patients, PNET patients and Others were more likely to have Medium/High risk scores for Financial Strain Risk (6% vs 6.5% and 8.5%, respectively) and Food Insecurity (1.7% vs 3.8% and 3.2%) (Table). There was no statistically significant difference in median medical debt and need of financial assistance between the groups. Among PDAC patients, there were differences in distributions among race, primary language spoken, and patient electronic record access depending on Financial Risk categories. African American patients had the greatest proportion of Medium/High risk (12.9%) compared to Asian (4.4%) and White (5.8%) patients (P<0.001). Among patients with English as their primary language, 64.9% had Low Risk scores compared to 27.7% with other primary languages (P<0.001). Patients with electronic record access were more likely to report High Risk scores (6.9%) compared to those without access (1.6%). Conclusions: Per patient responses collected, PDAC patients presenting to our center have lower risk of financial strain and similar medical debt levels compared to the remainder of cancer patients. Among PDAC patients, higher financial strain was experienced by non-whites (7.9% vs 5.8%). Diagnosis PDAC (N=2607) PNET (N=449) Other (N=84983) p value Current Financial Risk (Grouped) < 0.001 - Low Risk 1662 (63.8%) 304 (67.7%) 59298 (69.8%) - Medium/High Risk 157 (6.0%) 29 (6.5%) 7209 (8.5%) - Unknown/Missing 788 (30.2%) 116 (25.8%) 18476 (21.7%) Food Insecurity Risk < 0.001 - Low Risk 1764 (67.7%) 308 (68.6%) 63235 (74.4%) - Medium Risk 45 (1.7%) 17 (3.8%) 2703 (3.2%) - Unknown/Missing 798 (30.6%) 124 (27.6%) 19045 (22.4%) Median Active Debt in USD 1102.230 1020.010 1141.135 0.593

Introduction: Diffuse Large B-cell Lymphoma (DLBCL) are aggressive B-cell non-Hodgkin lymphomas (NHL). One particular subtype, Primary Mediastinal B-cell Lymphoma (PMBCL), is often grouped with DLBCL, but it possesses distinct biological and clinical characteristics. While initial therapy successfully cures approximately two-thirds of patients (pts), those who do not respond or experience progression within the first two years have a poor prognosis despite novel cellular therapies and bispecifics and ultimately succumb to their disease. There is a pressing need for more effective therapeutic approaches in this patient population. Recent advances in the understanding of DLBCL pathogenesis have led to the targeting of various signaling pathways, including the PI3K-AKT-mTOR pathway. One such drug, copanlisib (C), a pan-PI3K inhibitor with potent PI3K-α/PI3K-δ inhibition, exhibited activity in both indolent and aggressive NHL. In preclinical studies using a DLBCL mouse model, treatment with C effectively reduced the immunosuppressive tumor-infiltrating T-regulatory cells (Tregs). Moreover, when combined with a surrogate anti-mouse programmed death -1 (PD-1) blocker, C demonstrated significant in vivo responses (75%) compared to the monotherapy groups (0%). These findings support the rationale for exploring the combination of nivolumab, a PD-1 blocker, and copanlisib (C-N) in DLBCL. Thus, a phase 2 prospective study has been developed, focusing on two relapsed/refractory (RR) cohorts (DLBCL and PMBCL), treated with the combination of C-N. A prespecified interim analysis was planned upon enrollment of 14 pts. Herein, we report outcomes of the 12 enrolled pts, as the study was halted prematurely due to a safety signal deemed possibly related to the combination. Study design: C 60 mg was given intravenously on days 1, 8, and 15 during cycles 1-8, and on days 1 and 15 in subsequent cycles. N 240 mg IV was given on days 1 and 15 during cycles 1-8, and 480 mg on day 1 on subsequent cycles. Each treatment cycle is 28 days. Therapy was given for up to 2 years, as long as there is no disease progression or unacceptable side effects. The primary objective of the study is to determine the ORR, which includes complete and partial responses (CR+PR). Secondary objectives include evaluating the safety of the combination, as well as assessing progression-free survival (PFS), duration of response (DOR), CR, and overall survival (OS). The study plan was to enroll a maximum of 106 pts, including a safety cohort of 6 pts. The study received funding from Bayer and conducted through NCI-CTEP (NCI Protocol #10193; NCT03484819). Results: Twelve pts who received at least one cycle of C-N were included in this analysis. Pt characteristics are illustrated in table 1. All enrolled pts had DLBCL histology. Only one patient received a prior autologous stem cell transplant. Interestingly 4/12 received prior chimeric antigen receptor T-cell therapy (CART). Of the 12 enrolled pts, seven were evaluated for response. The ORR was 25% (3/12) (95% CI: 5 - 57%), all CR. The median number of cycles received was 2.5 (range 1-24) with two pts receiving 23 and 24 cycles. Observed grade 3 and higher adverse events (AEs) were as follows: non-hematologic AEs in 10/12 (83.3%), while hematologic AEs were seen in 5/12 (41.7%) pts. A relatively higher incidence of cardiac events (4/12) were noted including one cardiac arrest after one cycle of therapy, and four atrial fibrillation events, all grade 3, but only two were deemed possibly attributed to therapy. The cardiac arrest was deemed unrelated to therapy. Conclusions: C-N combination had modest clinical activity in pts with R/R DLBCL with some prolonged responses. However, due to the relatively high number of cardiac events and the changing therapeutic landscape with recent approvals, a decision was made to halt the study. These findings likely reflect possibly older and sicker patient population. Biomarker studies for predictors of response are under consideration.

9093 Background: Pembrolizumab interrupts PD-1/-L1 interaction and is efficacious in many cancers. However, resistance invariably emerges in the majority of patients. Potential mechanisms include activation of compensatory pathways. The inhibition of sonic hedgehog signaling (sHH) was previously shown to induce intra-tumoral (IT) infiltration by CD4+, CD8+ and HLA-DR class II cells. Our preclinical data showed sHH inhibitor enhanced IT penetration by monoclonal antibodies and induced PD-L1 expression. We conducted a phase I study using a novel sequential pulse dosing of sonedegib followed by pembrolizumab in aST with an expansion cohort to determine the maximum tolerated dose (MTD), tolerability and preliminary efficacy. Methods: The dose escalation utilized a 3+3 design to determine the MTD and proceeded to expansion cohort upon determination of the MTD. Patients enrolled to each dose level were observed for dose limiting toxicities (DLTs) during the 1st cycle. The expansion cohort consisted of NSCLC and head/neck squamous cell carcinoma (HNSCC) previously treated by anti-PD1/-L1. The recommended phase 2 dose (RP2D) was determined following the review of the toxicity profile of the combination from all cycles. The study treatment consisted of sonidegib oral daily from day 1 to 8 and pembrolizumab I.V. 200 mg on day 8 on an every 3-week cycle. The sonidegib dose levels explored were 400, 600 and 800 mg. Archival tumor and blood specimens were collected for correlative studies. Adverse events (AEs) were categorized and graded per CTCAE v5.0, and tumor response by RECIST v1.1. Results: The study enrolled a total of 33 patients and 29 received treatment (13 in escalation and 16 in expansion), including patients with NSCLC, HNSCC, skin cancer, gastric cancer and melanoma. The enrollment to the NSCLC cohort is complete and HNSCC continues. No DLT was encountered during dose escalation and the MTD was not reached. The highest planned dose level was selected to proceed to expansion (sonidegib 800mg days 1-8 in combination with pembrolizumab I.V. 200 mg on day 8 on an every 3-week cycle). The expansion cohort proceeded to enroll 15 patients evaluable for AEs (10 NSCLC and 5 HSNCC). Grade 3 and above treatment-related AEs across all patients were hyperglycemia, fatigue, dyspepsia, abdominal pain. The mature efficacy data will be reported at the meeting. Conclusions: The study successfully determined the RP2D of sonidegib when dosed sequentially with pembrolizumab in advanced solid tumors. The AE profile of the combination is similar to that for respective agents given individually. The efficacy data among anti-PD1/-PDL1-treated NSCLC will be reported at the meeting. Clinical trial information: NCT04007744 .