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34 Background: The American Society of Clinical Oncology (ASCO) and the Friends of Cancer Research (FCR) published a joint statement addressing clinical eligibility for characteristics lacking adequate representation in recent studies (Kim et al., Clin Cancer Res 2021). Herein, we aimed to identify the frequency of other potentially excessive exclusion criteria in the context of metastatic prostate cancer. Methods: The eligibility criteria of advanced prostate cancer studies with start dates between June 30, 2012 and June 30, 2022 were identified through Clinicaltrials.gov. MeSH (Medical Subject Headings) terms in our query were “(metastatic OR advanced OR stage IV OR unresectable) AND (prostate cancer OR prostate adenocarcinoma)”. Our study included trials conducted worldwide and examined patients aged 18 and over in phase I-III trials. To narrow the scope of study, trials including more than one cancer type (basket trials) as well as those focusing on radiation therapy were not included in the study. Descriptive statistics were used to determine the frequency of eligibility criteria while the Fisher’s exact test or chi-square test were performed to demonstrate association between type of treatment and exclusion criteria. Results: 265 of 699 (37.9%) clinical trials within the specified search had sufficiently available data for evaluation. Of these, 136 (51.3%), 51 (19.2%), 26 (9.8%), 20 (7.5%), 19 (7.2%), and 7 (2.6%) of trials investigated treatment with combination therapy, hormone therapy, targeted therapy, immunotherapy, radioligand therapy, and chemotherapy, respectively. The most common ASCO-FCR-cited exclusion criteria in the studies were brain metastases (161/265, 60.8 %), HIV positivity (123/265, 46.4%), HBV/HCV positivity (122/265, 46.0%), and concurrent malignancies (41/265, 16.6%). Statistically significant relationships were identified between type of treatment along with status of brain metastases, HIV, and HBV/HCV (p=0.011

612 Background: A consensus statement from the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (FCR) collaboration highlights the importance of expanding eligibility criteria in cancer trials to more accurately reflect the real-world population (Kim et al., Clin Cancer Res 2021). We sought to characterize use of overly restrictive eligibility criteria in renal cell carcinoma (RCC) trials in the context of ASCO-FCR recommendations. Methods: Studies containing the MeSH terms “(metastatic OR advanced OR stage IV or unresectable) AND (kidney cancer OR renal cell carcinoma OR renal cell cancer)” from June 30, 2012 to June 30, 2022 were identified on the ClinicalTrials.gov platform. Our search query’s inclusion criteria identified international studies examining adult patients aged ≥ 18 in phase I-III trials. Exclusion criteria comprised pan-cancer studies, trials involving localized treatments, radiation therapy, and prognostic tools. Descriptive statistics were used to characterize the frequency of restrictive eligibility criteria across studies, while Fisher’s exact test or chi-square test were utilized to determine the association between treatment type and exclusion criteria. Results: The content of 423 RCC trials were analyzed, of which 112 (26.5%) had adequate data available. 48 (42.9%), 44 (39.3%) and 18 (16.1%) studies examined combination therapy, targeted therapy, and immunotherapy, respectively. The presence of HIV positivity, HBV/HCV positivity, brain metastases, and concurrent malignancies accounted for the most frequently cited exclusionary criteria, seen in 83/112 (74.1%), 60/112 (53.6%), 37/112 (33.0%), and 9/112 (8.0%) studies respectively. Differences in the use of HIV positivity (p

662 Background: Mounting data suggests that dietary modification and supplement use, including probiotics, may modulate outcomes with immunotherapy in cancer therapy (Spencer CN et al. Science 2021; Dizman N et al. Nature Medicine 2022). For the first time, we sought to quantify the use of these measures among patients with metastatic renal cell carcinoma (mRCC). Methods: An online survey was administered by Kidney Cancer Research Alliance (KCCure), a non-profit patient advocacy group, between July 22 and Sept 22 to a patient mailing list (N=1,532). Only patients diagnosed with mRCC and under active systemic therapy were included for analysis in the current study. Select questions were directed at dietary modification patterns and supplement usage. Patients were additionally surveyed regarding out-of-pocket spending patterns related to supplement purchases and to what extent they shared information about their supplement intake with their physicians. The student's t-test and Chi-square test were used to compare sociodemographic characteristics between participants who did and did not report supplement intake. Results: Out of 1,062 patients with renal cell carcinoma who participated in this survey, 289 met the inclusion criteria (M:F, 145:143). The median age was 61. The majority of patients identified themselves as white (91%), were from the US (86.8%), and had completed a bachelor's degree (52.9%). 21.1%, 46.1%, and 32.6% lived in urban, suburban, and rural locations, respectively. The most common reported first-line treatments were nivolumab/ipilimumab (32.4%) and axitinib/pembrolizumab (13.1%). 22.4% of respondents reported spending >$100/month on supplements, and 8.3% reported spending >$250/mo. Dietary modifications following a cancer diagnosis were reported by 34.9% of respondents, out of which 19.8% followed the Mediterranean diet and 18.8% adopted a ketogenic diet. 50.8% of respondents reported supplement intake. The most widely utilized supplements were cannabidiol (CBD) oil/marijuana, probiotics, and Vitamin C, reported by 28.0%, 24.2%, and 18.6% of respondents, respectively. 83.4% of respondents noted that they consistently report supplement usage to their physicians. There were no statistically significant associations between supplement use and age, sex, living area, or education. Conclusions: A substantial proportion of patients with mRCC use dietary modification and supplements as an adjunct to their antineoplastic treatment. Interventions such as probiotic use and ketogenic diets, which are the subject of a prospective study in mRCC (NCT05119010; NCT05122546), may already be used by many patients. More careful attention to nutrition and supplement use in clinical trial candidates may minimize the impact of these potential confounders.

453 Background: American Society of Clinical Oncology (ASCO) and the Friends of Cancer Research (FCR) underscored the need to broaden eligibility criteria in cancer trials to increase patient accrual, expand access to investigational treatments, and enhance generalizability of study results (Kim et al., Clin Cancer Res 2021). While eligibility criteria intend to prioritize patient safety and define a specific study population, these criteria are often based on outdated standards and may not be reflective of real-world practice. Our study aimed to characterize the proportion of aUC trial eligibility criteria according to the ASCO-FCR statement. Methods: Protocols indexed on ClinicalTrials.gov with start dates from June 30, 2012 to June 30, 2022 were evaluated. MeSH terms used in our query were “(metastatic OR advanced OR stage IV OR unresectable) AND (bladder cancer OR upper tract urothelial carcinoma OR upper tract urothelial cancer)”. International studies enrolling patients aged 18 and over in phases I-III were included. Studies examining multiple cancer types as well as those involving localized treatments (e.g., surgery or ablation), radiation therapy, and prognostic tools were excluded. Analyses of eligibility criteria focused on those highlighted in the ASCO-FCR statement; descriptive statistics were used to define the frequency of eligibility criteria and chi-square and Fisher’s exact test were used to determine their association with treatment type. Results: Overall, 205 urothelial cancer trials were assessed, with 37 (18.0%) having publicly accessible data. Of these, 13 (35.1%) evaluated combination therapy, 11 (29.7%) evaluated immunotherapy, 8 (21.6%) evaluated targeted therapy, and 5 (13.5%) evaluated chemotherapy. HIV positivity, HBV/HCV positivity, brain metastases, and concurrent malignancies were found to be exclusion criteria in 89.2% (33/37), 56.8% (21/37), 35.1% (13/37), and 5.4% (2/37) of studies, respectively. While brain metastases, concurrent malignancies, and HBV/HCV positivity were found to be independent of the class of therapy, a statistically significant association was observed with HIV positivity. Specifically, trials evaluating combination therapy (100.0%), immunotherapy (100.0%) and targeted therapy (87.5%) more frequently included HIV positivity as an exclusion criterion as compared to chemotherapy trials (40.0%). Conclusions: A modest percentage of a UC studies from the last decade were observed to report overly restrictive eligibility criteria as defined by the ASCO-FCR statement. HIV positivity and HBV/HCV positivity were commonly identified exclusion criteria, despite limited evidence that these criteria significantly impact drug efficacy and tolerability. Reassessing and updating eligibility criteria will ensure that the resulting data is more reflective and inclusive of a real-world population.

165 Background: Small cell/neuroendocrine cancers irrespective of origin share aggressive phenotypes. Pembrolizumab (MK-3475) is a humanized antibody targeting programmed cell death protein 1 (PD-1) that has shown activity against small cell lung cancers. Preclinical studies showed molecular commonality amongst small cell cancers across multiple tissue types. This study evaluated the safety and efficacy signals of pembrolizumab and chemotherapy in patients with small cell/neuroendocrine cancer of the prostate and urothelium. Methods: Patients with locally advanced or metastatic small cell cancer of the bladder (cohort 1) and primary small cell or treatment-derived neuroendocrine prostate cancer (NEPC) (cohort 2) received pembrolizumab and standard of care chemotherapy (etoposide and cisplatin/carboplatin for cohorts 1 and 2, with option of docetaxel and carboplatin for cohort 2) with maintenance pembrolizumab for 2 years until unequivocal progressive disease or unacceptable toxicity. Primary endpoint was to estimate ORR, PFS, and OS compared to historical controls as well as safety and tolerability. Targeted gene mutation sequencing as well as sequential single cell sequencing of peripheral blood mononuclear cells (PBMCs) for immune profiling as well T cell receptor (TCR) repertoire was performed. Results: 14 patients were enrolled (7 cohort 1, 7 cohort 2) with mean age 64.9 (range 53 to 81). ORR was 43% (95% CI: 0.06, 0.80) overall and within each cohort. PFS rate at 12 months was 64% (95% CI: 0.44,0.95) across cohorts, 86% (95% CI: 0.63,1.00) within cohort 1, and 43% (95% CI: 0.18,1.00) within cohort 2. OS rate at 12 months was 79% (95% CI: 0.60,1.00) across cohorts, 86% (95% CI: 0.63,1.00) within cohort 1, and 71% (95% CI: 0.45,1.00) within cohort 2. 4 patients in cohort 1 with locally advanced disease underwent radical cystectomy, with no PD at a mean follow up of 29 months. Grade 3 or higher AEs occurred in 87% of patients, while 40% of patients experienced grade 3 or higher AEs related to pembrolizumab. In 12 patients where tissue was sufficient, all patients had genomic alterations in either p53 (75%) or Rb (58%). Single cell sequencing showed progressive enrichment of CD8+ T cells with clonal expansion of specific TCRs in responding patients. Conclusions: In patients with locally advanced or metastatic small cell/neuroendocrine prostate and bladder cancers, combination pembrolizumab with standard of care chemotherapy and maintenance pembrolizumab showed promising efficacy with tolerable adverse events. Clinical trial information: NCT03582475 .

510 Background: Small cell/neuroendocrine cancers irrespective of origin share aggressive phenotypes. Pembrolizumab (MK-3475) is a humanized antibody targeting programmed cell death protein 1 (PD-1) that has shown activity against small cell lung cancers. Preclinical studies showed molecular commonality amongst small cell/neuroendocrine cancers across multiple tissue types. This study evaluated the safety and efficacy signals of pembrolizumab and chemotherapy in patients with small cell/neuroendocrine cancer of the prostate and urothelium. Methods: Patients with locally advanced or metastatic small cell cancer of the bladder or upper urinary tract (cohort 1) and primary small cell or treatment-derived neuroendocrine prostate cancer (NEPC) (cohort 2) received pembrolizumab and standard of care chemotherapy (etoposide and cisplatin/carboplatin for cohorts 1 and 2, with option of docetaxel and carboplatin for cohort 2) with maintenance pembrolizumab for 2 years until unequivocal progressive disease or unacceptable toxicity. The primary endpoint was to estimate ORR and PFS compared to historical controls as well as safety and tolerability. Pretreatment targeted gene mutation sequencing was performed. Results: 14 patients were enrolled (7 cohort 1, 7 cohort 2) with mean age 64.9 (range 53 to 81). ORR across cohorts was 43% (95% CI: (0.17, 0.69)), and 43% (95% CI: (0.06, 0.80)) within each cohort. PFS rate at 12 months (proportion of patients who have not progressed at 12 month) was 61% (95% CI: (0.40,0.95)) across cohorts, 86% (95% CI: (0.63,1.00)) within cohort 1, and 36% (95% CI: (0.12,1.00)) within cohort 2. 3 patients in cohort 1 with locally advanced disease exhibited SD and underwent radical cystectomy, with one patient pT0 and no PD at a mean follow up of 20 months. Grade 3 or higher AEs occurred in 71% of patients, while 29% of patients experienced grade 3 or higher AEs related to pembrolizumab. No patients died or discontinued therapy secondary to adverse treatment effects. In 12 patients where tissue was sufficient, all patients had genomic alterations in either p53 (75%) or Rb (58%). Of the 5 available patients with NEPC, 60% had alternations in DNA damage response genes. Conclusions: In patients with locally advanced or metastatic small cell/neuroendocrine prostate and bladder cancers, combination pembrolizumab with standard of care chemotherapy and maintenance pembrolizumab showed promising efficacy with tolerable adverse events. Clinical trial information: NCT03582475.

517 Background: Many patients with muscle-invasive bladder cancer are not ideal candidates for chemotherapy or radical cystectomy. Moreover, local progression may further impair quality of life. Bladder preservation with maximal transurethral resection of bladder tumor (TURBT) and stereotactic body radiotherapy (SBRT) is a viable treatment option for such patients, offering durable local control while potentiating the effect of immunotherapy. Herein, we report on the safety profile of SBRT in combination with durvalumab (anti-PDL1) and tremelimumab (anti-CTLA4) in the safety lead-in cohort of an institutional Phase II trial for cisplatin-ineligible, unresectable locally advanced or metastatic bladder cancer patients. Methods: Patients with locally advanced or metastatic urothelial carcinoma, who were unwilling or unable to undergo radical cystectomy and/or systemic chemotherapy were eligible. Patients received maximal TURBT, followed by durvalumab 1500mg IV every 4 weeks and bladder SBRT 33Gy in 5 fractions between the first 2 cycles. After 6 such patients did not experience a dose limiting toxicity, tremelimumab 75mg IV was added for cycles 1-2. Patients were followed with CT Chest/Abdomen/Pelvis and cystoscopy every 3 months. Treatment-related adverse events (TRAEs) were assessed per CTCAE 5.0 and progression was assessed per RECIST 1.1. Results: Between January 2019 and May 2020, 10 patients received TURBT followed by SBRT and durvalumab (Age 73-96, 3 Female, 7 ECOG 1, 3 ECOG 0). Five patients had localized disease and 5 had nodal or distant metastases. Median cycles of durvalumab was 12.5 (2-13), and 4 patients received 2 cycles of tremelimumab. At a median follow-up of 16.8mo (6.4-30mo), there were 2 Grade 3+ immunotherapy-related TRAEs (1 Grade 3 lipase elevation self-resolved, 2 Grade 3 myositis treated with steroids). The most common TRAEs of any grade included pancreatic enzyme elevation (3 patients), rash (3 patients), and urinary symptoms related to RT (3 patients). Disease control rate 70% and local control was 90%. There were 3 non-treatment related deaths. Conclusions: Bladder SBRT with durvalumab and tremelimumab was well tolerated and demonstrated promising local control in the safety lead-in cohort. Clinical trial information: NCT03601455.

6083 Background: Racial outcome disparities have been observed in head and neck cancer with diminished survival for black patients compared to whites. The etiology of this disparity appears to be m...