Léonard, A.

TPS2689 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, existing FDA approved companion diagnostic biomarkers like PD-L1, dMMR/MSI-H and TMB have low accuracy in predicting response. Ex vivo cytokine profiling of live tumor samples has shown promise as an improved means of predicting response to PD-1 blockade (Voabil, et al. Nat Med. 2021), but this approach has been limited to tumor resections given the need for large amounts of tissue. Here we present three clinical trials that leverage a novel approach using limited tissue from a single core needle biopsy (CNB) (20 gauge or larger). A sequential ex vivo treatment strategy is used, eliminating the need for a separate control arm and addressing challenges with tumor heterogeneity, particularly in CNBs where tissue is limiting. Using a specialized instrument, CNBs are cut into live tumor fragments (LTFs) which are viable in culture and retain the native tumor microenvironment, enabling cytokine profiling in response to ICI treatment ex vivo. Methods: ELEPHAS-01 (NCT05478538), ELEPHAS-02 (NCT05520099) and ELEPHAS-04 (NCT06349642) are observational prospective clinical trials initiated to characterize the accuracy of this approach for predicting ICI response. Over 750 patients that are being considered for standard of care (SOC) ICI therapy in the metastatic/relapse or neoadjuvant setting will be enrolled (Table). Fresh live CNBs are collected prior to treatment start and processed within 24 hrs enabling prediction of results within 72 hrs of receipt. LTFs are treated using a strategy where control (IgG) and SOC ICI treatments are performed sequentially on the same tissue in a single well. Changes in the cytokine secretion rates are then compared between ICI and control to characterize immunotherapy response. Additionally, tissue viability and tumor content measurements are used to assess tissue quality. Clinical response is measured using pathologic response in patients receiving neoadjuvant ICI therapy, while RECIST v1.1 is used in all other patients. The primary objective of these trials is to determine the platform’s ex vivo accuracy (e.g., sensitivity, specificity) for predicting clinical response to ICIs and comparing it to the accuracy of PD-L1, dMMR/MSI-H and TMB. Clinical trial information: NCT06349642 , NCT05478538 , NCT05520099 . ELEPHAS-01 (Lung) ELEPHAS-02 (Hoosier) ELEPHAS-04 (Mayo) Setting Metastatic & recurrent Metastatic & recurrent Metastatic, recurrent & neoadjuvant Tumor type Lung Bladder, kidney, colorectal, head and neck, lung, melanoma, endometrial Metastatic/recurrent: lung, skin, esophageal, cervical, endometrial, colon, liver, kidney, bladder Neoadjuvant: breast–TNBC, lung Enrollment as of 1/27/2025 26 44 20 Est. total enrollment 216 216 324 Clinical endpoints RECIST v1.1 RECIST v1.1 RECIST v1.1 & Pathologic response at surgery

Abstract Introduction Testosterone deficiency affects approximately 4-5 million men in the United States. The bidirectional association between testosterone deficiency and metabolic syndrome has been well-established. The diagnosis of testosterone deficiency should serve as a trigger for medical evaluation of other comorbidities. Furthermore, male sex is an independent predictor of decreased routine health maintenance; men are 40% less likely to have a primary care provider (PCP) compared to women in the United States. Thus, many patients who present to the urologist for symptomatic testosterone deficiency might have undiagnosed or poorly managed comorbidities coupled with a lack of a PCP. Objective We sought to investigate the impact of offering primary care access within an integrated Men’s Health Center to men presenting for initial evaluation of symptomatic testosterone deficiency. Methods This is a retrospective single institution study. All new patients presenting with testosterone deficiency between October 2019 and October 2022 were offered evaluation by a PCP within a university-based Men’s Health Center. Patients who were seen by the PCP underwent standard health screening and blood work including a lipid profile, liver function testing, and diabetes screening with hemoglobin (Hgb) A1c. All data were collected from the electronic medical record and deidentified. Institutional review board (IRB) exemption was obtained. Variables collected for analysis included age, race, body mass index (BMI), testosterone level on presentation, prior access to a pre-existing PCP, and number of visits attended with our PCP. Outcomes measured include new diagnoses made by the PCP and referral patterns to other specialties. All statistical analysis was conducted utilizing SPSS version 28. Results 81 men were evaluated over the 3-year study period. Median age was 49.0 (range: 21.2-93.7 years). 48 men (59%) established continuity of care and were seen by our PCP for more than 1 visit. 33 men (41%) did not have a pre-existing PCP. Older men were significantly more likely to have a pre-existing PCP (OR 1.06 [95% CI: 1.02-1.10], p<0.001). Hispanic men were significantly less likely to have an existing PCP (OR 0.16 [95% CI: 0.03-0.84], p=0.01). Newly diagnosed comorbidities included hypertension (41%), obesity (37%), hyperlipidemia (27%), obstructive sleep apnea (OSA; 25%), depression (23%), and diabetes (14%). 41 patients (51%) were prescribed a new medication. 21 patients (26%) were referred to nutrition, with mean BMI decrease of 1.75. 26 patients (32%) underwent sleep medicine evaluation for OSA. 27 (33%) and 37 patients (46%) received a flu vaccination and immunization updates. 11 patients (14%) were referred for screening colonoscopy. Patients who established continuity of care were significantly more likely to be treated for a new diagnosis (p<0.001) and receive a flu vaccination (p=0.007; Table 1). Conclusions This is the first report of integrated primary care and urology evaluation for testosterone deficiency. This comprehensive model results in improved outcomes including increased access to subspecialty referrals, objective weight loss, treatment of new diagnoses, updated immunizations, and cancer screening. Further studies are needed to assess reproducibility across other institutions, cost-effectiveness of this model, and patient satisfaction. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific, Endo Pharmaceuticals.