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Venous thromboembolism (VTE) is an important cause of morbidity and mortality in the United States (US). The increasing rates of VTE in the US resulted in the surgeon general issuing a call to action to reduce VTE in 2008. The objective of our study was to analyze the national trends of inpatient VTE in the US from 2004 to 2013 (5 years before and after 2008). We used the dataset National Inpatient Sample, Healthcare Cost and Utilization Project and measured trends of inpatient VTE by annual % change using joinpoint regression software. From 2004 to 2013 the National Inpatient Sample contained data on 78 million hospitalizations (weighted n = 385 million). In these 1.6 million had a diagnosis of VTE (2.0%, weighted n = 7.7 million) including 1.2 million with deep venous thrombosis (DVT) (1.53%, weighted n = 5.9 million) and 588,878 with pulmonary embolism (PE) (0.74%, weighted n = 2.8 million). Joinpoint regression analysis showed that rates of DVT and PE are increasing consistently from 2004 to 2013(1.27% to 1.80% for DVT and 0.52% to 0.92% for PE). The increasing rates of DVT and PE were consistent in all subgroups except few exceptions. In conclusion inpatient VTE rates continue to rise even after 5 years from the surgeon general's a call to action except in certain high-risk patients. Further research is needed to curb the VTE in patients especially among those perceived to be at lower risk of VTE.

e16540 Background: Neo-adjuvant cisplatin-based chemotherapy (NAC) is considered standard of care for patients with locally advanced disease. However, ̃40% of patients are cisplatin ineligible (CI) due to renal insufficiency, hearing loss or poor performance status. Gemcitabine and carboplatin (GCa) has limited success in this setting. Patients usually proceed directly to cystectomy without realizing the potential survival benefit afforded by NAC. Intravenous ascorbate (vitamin C) administration (IVC) has been shown to improve the efficacy of carboplatin and gemcitabine-based therapy in other models. This single-arm, Simon 2-stage, window of opportunity trial included IVC with single cycle GCa to evaluate pathologic downstaging. We report on the interim first stage analysis of 12 patients. Methods: Patients with newly diagnosed CI-MIBC were enrolled and received single cycle GCa and IVC titrated to peak plasma concentration of 350 to 400 mg/dL (̃20 mM) for 21 days followed by cystectomy at 4-6 weeks from initiation of treatment. The primary outcome is pathological stage at cystectomy. Patients are then followed per NCCN guidelines with standard of care bloodwork, physical exam and imaging studies until progression and/or death. QOL is being evaluated by Functional Assessment of Cancer Therapy-Bladder (FACT-Bl). Results: All 12 patients completed GCa/IVC with 11 having had a cystectomy and 1 pending surgery. Pathological downstaging (yp < T2) was noted in 4 patients with 3 CRs (ypT0N0Mx) and 1 with residual ypTisN0Mx only. Of note, 1 CR was seen in a patient with locally advanced plasmacytoid variant. Participants tolerated treatment well with minimal treatment related AE/SAEs. Conclusions: Interim analysis of GCa-IVC NAC shows good tolerability with > 36% rate of downstaging. Of those with a pathological response, 75% achieved a CR. Continuation criteria has been met for stage 2. FACT-BI analysis and clinical follow up is ongoing and will be reported at study completion. Clinical trial information: NCT04046094.

6542 Background: Access to health care including clinical trials (CT) leading to paradigm-changing cancer treatments are critical for high quality cancer care and equity in society. In this report, we highlight methods in accruing to ETCTN wherein underrepresented rural, low-income, and racial minorities comprise >50% of enrollment. Methods: University of Kansas Cancer Center (KUCC) is one of eight National Cancer Institute (NCI) designated cancer centers awarded CATCH-UP.2020 (CATCH-UP), a congressionally mandated P30 supplement to enhance access for minority/underserved populations to ETCTN precision medicine CT. KUCC catchment area is 23% rural by Rural Urban Continuum Codes (RUCC); almost 90 % of counties are designated primary care HPSA’s (Health Professional Shortage Areas). KUCC Early Phase and Masonic Cancer Alliance (rural outreach network) partnered to operationalize CATCH-UP. We engaged disease-focused champion investigators in disease working groups and MCA physicians who selected scientifically sound CT that fit catchment area needs. Patient and Investigator Voices Organizing Together, a patient research advocacy group provided practical feedback. MCA navigator coordinated recruitment. Telehealth was used for rural patients that would have a significant distance to travel just to be screened. Results: CATCH-UP was initiated in September 2020. Twenty-eight CT were activated, many in community sites. Average activation time was 81 days. Delays were mainly from CT amendments. KUCC enrolled the first patient in the CATCH-UP program. In 6 months, we met accrual requirements (24/year, 50% minorities). During first year, we enrolled 47 (>50% minorities), an increase of 680% from our average accrual of 6/year (>50% minorities) in ETCTN through Early Drug Development Opportunity Program (2016-2020). To date, we have enrolled 61, 54% from rural, HPSA, race and other minorities. Although the proportion of minorities did not change but remained high, this funding allowed us to substantially increase the number of patients from a catchment area with high proportion of geographically and socioeconomically underserved minorities given access to early phase CT through ETCTN. Conclusions: Amid COVID-19 pandemic, the NCI CATCH-UP program and methods we used allowed access to novel therapies for rural, medically underserved, and other minority groups. Funded by NIH: 3P30CA168524-09S2.

e16557 Background: Fosciclopirox (F) is being developed for the treatment of non-muscle invasive (NMIBC) and muscle invasive (MIBC) bladder cancer. F is a prodrug which is rapidly and completely metabolized in blood to its active metabolite, ciclopirox (CPX). In preclinical models of bladder cancer, CPX acts in part as a γ-secretase inhibitor by binding to γ-secretase complex proteins Presenilin 1 and Nicastrin, resulting in Notch and Wnt inhibition. The F Recommended Phase 2 Dose (RP2D), 900 mg/m2 administered IV over 20 minutes, was identified in the Phase 1 dose escalation trial (NCT03348514) in advanced solid tumor patients. Methods: The F RP2D was investigated in two early phase NMIBC and MIBC clinical proof of concept trials. In NCT04608045, neoadjuvant F was administered as monotherapy in cisplatin-ineligible (C-I) MIBC patients and in combination with gemcitabine + cisplatin in chemotherapy-eligible (C-E) MIBC patients. Clinical stage was assessed in pre-treatment (TURBT/CT) and post-treatment pathological state determined at radical cystectomy, (RC). The steady-state plasma and urine pharmacokinetics of F were also characterized. In NCT04525131, F was administered once daily for five days prior to TURBT. Pre- and post-treatment (at TURBT) bladder tumor samples underwent single cell sequencing to identify treatment effects on gene expression. Plasma, urine, and bladder tumor concentrations of F and its metabolites were determined in samples collected at TURBT. Results: Five C-E and 4 C-I MIBC patients received neoadjuvant F prior to RC. Twelve NMIBC patients received F prior to TURBT. There were no treatment-related serious adverse events observed in either study. Each patient experienced at least one treatment-emergent adverse event (TEAE), none of which resulted in study discontinuation. The most common TEAEs were nausea, fatigue, and constipation. Pathologic downstaging (< ypT2) of bladder tumors was observed in 3 C-E MIBC patients with 2 CRs (ypT0). Two of 4 C-I patients had evident clinical response by CT scan with only microscopic residual ypT2 disease. Treatment-related changes in expression of Notch 1, Notch 2, Hes 1, Hey-1, c-Myc, ß-catenin and survivin were observed in the majority of NMIBC patients. F disappeared from plasma within 2 hours of administration. The mean CPX elimination half-life of CPX, apparent systemic clearance, and volume of distribution values were 8.8 hours, 46 L/hr and 549 L, respectively. Mean plasma, tumor and urine concentrations of CPX at TURBT were approximately 27, 9 and 100 µM, respectively. Conclusions: To date, fosciclopirox is well tolerated and achieves sufficient systemic, tumor, and urine CPX exposure at the RP2D. Evidence of target inhibition was demonstrated in NMIBC tumors and preliminary signs of clinical activity observed in MIBC patients. Safety and efficacy trials are planned to confirm and expand findings in NMIBC and MIBC patients. Clinical trial information: NCT04608045; NCT04525131.

4529 Background: Immune checkpoint blockade has revolutionized mRCC Tx, but primary and acquired resistance continues to result in poor patient outcomes. OX40 (CD-134) mediates IO resistance. Co-stimulatory OX40 (CD-134) activates exhausted T-cells. OX40 activation in dendritic cells increases the proliferation, effector function, and survival of T cells. PFOX is an agonist for OX40. We hypothesized that PFOX + the VEGFR inhibitor Axi would improve outcomes vs. Axi in patients (pts) with mRCC after IO Tx. Methods: Pts with predominantly clear cell mRCC were stratified for MSKCC risk groups then randomized 1:1 to Axi 5mg po bid plus PFOX 0.3mg/kg iv (Arm 1) or placebo (PL) iv (Arm 2) on Day 1 of a 2-week cycle. The primary endpoint was progression free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DOR) per RECIST v1.1, and safety/tolerability. A prespecified interim analysis (IA) tested PFS at a 1-sided P < 0.02 when ≥ 33 events were observed. Results: Between February 2018 and October 2021 a total of 59 pts were randomly assigned and treated with Axi+PFOX (N = 29) or Axi+PL (N = 30). Pt and disease characteristics are summarized in the table. As of October 2021, 38 PFS events had occurred, 19 on each arm. The IA rejected the hypothesis of added efficacy for PFOX with a p of 0.0089. Subsequently the study was closed to new accrual. At a median follow up of 13.4 mo, median PFS was 13.1 (6-15.8) months (mo) for Arm 1 and 8.5 (5.5-11) mo for Arm 2 (HR = 0.85 [95% CI: 0.45-1.60] p = 0.61). After adjusting by MSKCC risk group and prior lines of Tx, HR = 0.74 [95% CI: 0.38-1.46] p = 0.39. Median OS was not reached (adjusted HR = 0.71 [95% CI: 0.24-2.12] p = 0.54). ORR Arm 1: 31% PR, 52% SD, 14% PD, and Arm 2: 37% PR, 50% SD, 13% PD. Median DOR 9.1 (3.3-23.9) mo for Arm 1, and 7.5 (1.8-32.7) mo. for Arm 2. Rates of any grade Tx related adverse events (TRAEs; 93% vs 100%), including grade 3 or 4 TRAEs (66% vs 47%), in Arm 1 and Arm 2, respectively. 4 pts discontinued Tx due to TRAE, 3 in Arm 1 (1 grade 3 hypertension, 1 grade 2 stroke, 1 grade 3 bullous dermatitis) and 1 in Arm 2 (grade 4 ALT elevation). The most common TRAEs were diarrhea 52%, hypertension 52%, fatigue 41%, nausea 41% for Arm 1 and hypertension 67%, diarrhea 53%, fatigue 50% for Arm 2. Conclusions: In IO-pretreated mRCC pts, Axi + PFOX did not improve outcomes compared to Axi alone. Clinical trial information: NCT03092856. [Table: see text]

119 Background: Radium-223 is an α-emitting radioisotope that induces DNA double-strand breaks leading to cell death. In preclinical models, PARP inhibitors have shown efficacy as radiosensitizing agents. We designed a phase 1/2 trial to test the safety and efficacy of radium-223 + olaparib. Tissue based studies investigated homologous recombination repair (HRR) gene status. Methods: This was an open-label, multi-center, phase 1/2 study (NCT03317392) evaluating the dosing, safety and efficacy of radium-223 + olaparib. Eligible patients (pts) had mCRPC with ≥2 bone metastases without visceral metastases or lymphadenopathy > 4 cm. There was no limit on prior therapy. All pts had a baseline biopsy and archival tissue was collected when available. The phase 1 used a 3+3 dose escalation design with fixed dose radium-223 (55 kBq/kg IV every 4 weeks x 6). Dose level 1 (DL1) was olaparib 200 mg PO BID; DL2 was olaparib 300 mg PO BID. The primary objective was to determine the recommended phase 2 dose (RP2D). Secondary objectives included radiographic progression-free survival (rPFS) (PCWG3 criteria), PSA response (50% decline from baseline), and alkaline phosphatase response (30% decline from baseline). HRR gene status was determined using Oncopanel tissue profiling. Results: 12 pts were enrolled on the phase 1. Median age was 68 (range 59-81) years. Median prior lines of CRPC therapies was 2 (1-5), including 3 (25%) who had received prior chemotherapy and 12 (100%) a prior novel hormone therapy. The RP2D of olaparib was 200 mg BID when combined with radium-223. Overall, PSA response and alkaline phosphatase response were 16.7% (n=2) and 67% (n=8), respectively. Median follow-up was 6.5 (range 2.8, 11.8) months, and 6-month rPFS was 57% (95% CI: 25%, 80%). 9 patients had available tissue for Oncopanel testing (7 from baseline metastasis biopsy; 2 from archival prostate tissue). Two patients were identified to have pathogenic HRR gene alterations: 1 patient with a BRCA2 mutation with rPFS of 11.63 months, 1 patient with CDK12 mutation with rPFS 2.60 months (Table). Conclusions: We demonstrate that olaparib can be safety combined with radium-223 with RP2D of 200 mg BID. Though limited by sample size, we demonstrate prolonged disease control in a pt with a BRCA2 mutation receiving radium-223 + olaparib. Additional profiling from the currently accruing phase 2 study of radium-223 +/- olaparib will further elucidate biomarkers of response. Clinical trial information: NCT03317392. [Table: see text]

94 Background: CART-PSMA-02 is a multi-center, open-label, phase 1 trial evaluating the safety and feasibility of CART-PSMA-TGFβRDN T-cells (PSMA-CART) in patients (pts) with metastatic castration resistant prostate cancer (mCRPC). PSMA-CART are engineered to express a chimeric antigen receptor with specificity to PSMA and a dominant negative form of TGFβRII which renders PSMA-CART resistant to TGFβ-mediated immunosuppression. Herein, preliminary safety and efficacy results from this trial are reported. Methods: This is a 3+3 dose escalation study to determine the recommended phase 2 dose and schedule of PSMA-CART cells following lymphodepleting chemotherapy (LD) with cyclophosphamide and fludarabine. Results: As of October 2021, 9 pts were dosed. Two pts received 1-3x107 cells, 4 pts received 1-3x108 cells, and 3 pts received 0.7-1x108 cells with anakinra prophylaxis. Grade 1-2 CRS was observed in all pts receiving 1-3x108 cells and 2/3 pts who received anakinra prophylaxis. No pts developed CRS > G2. Two events of immune-effector cell associated neurotoxicity syndrome (ICANS) were observed (1 G2, 1 G5). Two pts experienced DLTs at dose level of 1-3x108, one of whom developed G5 events of ICANS and multi-organ failure (MOF) after receiving 30% of his fractionated dose (total dose = 0.9x108). This pt’s clinical course and autopsy findings were consistent with macrophage activation syndrome. The trial continued with a modified dose of 0.7-1x108 and the incorporation of prophylactic anakinra (100mg SC daily x7 doses). Another G5 event was observed, likely related to immune toxicity, with ferritin levels peaking at >100,000 ng/mL prior to death. Cause of death on autopsy was equivocal and contributing factors included metastatic prostate cancer, MOF and coagulopathy. Cytokine levels from both pts experiencing G5 events were elevated compared to all other pts (e.g., IL-6, sIL2RA, MIG/CXCL9, MIP1b/CCL4, IP-10/CXCL19, IL2 and IL1b). In pts receiving ≥ 0.9x108 cells (n=7), preliminary efficacy results demonstrated stable disease by RECIST v1.1 at day 28 (D28) in 4/5 evaluable pts. Decreases in serum PSA occurred in 4/7 pts with >50% decreases observed in 2/5 evaluable pts at D28. Conclusions: PSMA-CART has shown preliminary evidence of biological activity in the absence of clear indications of on-target/off-tumor toxicity. The exact mechanisms driving the severe immune-mediated toxicities in this study are currently unclear. While this study has been closed to further enrollment, ongoing research efforts are aimed at exploring patient specific factors, tumor microenvironment factors, and the PSMA-CART construct (including both functional components and armored modules) to design future constructs of PSMA-CART that will enhance the efficacy/safety profile and allow for continued study of this novel therapy in the clinic. Clinical trial information: NCT04227275.

Patient: Female, 64-year-old Final Diagnosis: Plasmacytoid urothelial carcinoma of the bladder Symptoms: Nausea • vomiting Medication:— Clinical Procedure: Cystoscopy Specialty: Oncology Objective: Rare disease Background: Plasmacytoid urothelial carcinoma (PUC) is a rare and aggressive variant of urothelial cancers. Herein, we report a patient with CDH-1 mutated PUC who presented with disseminated peritoneal metastasis and high levels of CA 19-9. Cases Report: A 65-year-old female presented to the hospital with vomiting, obstructive jaundice, and acute renal failure. Imaging studies showed bilateral hydronephrosis, bladder wall thickening without masses, and dilation of both common bile and pancreatic ducts without pancreatic masses. Carbohydrate antigen (CA) 19-9 was elevated at >17 000 U/mL. Repeated cystoscopies demonstrated no masses within the bladder, but with nodularity and inflamed mucosa, and random biopsies were obtained and showed PUC. Ascitic fluid cytology revealed meta-static PUC. A targeted exome next-generation sequencing (NGS) revealed pathogenic mutations in TP53, CDH-1, RB1, and ARIDA1A. The patient was debilitated, and hospice care was recommended. She passed away after 2 months of her initial presentation. Conclusions: PUC is a rare and aggressive histological variant of bladder cancer. Advanced stage at diagnosis and high relapse rates after treatment with cytotoxic regimens are common. At the molecular level, somatic alterations in cadherin-1 (CDH-1) gene seem to be characteristic. Exploring the molecular sphere of this disease is prudent to identify possible new therapeutic targets.

A recent study found that approximately 1 in every 6 patients hospitalized for the 1st episode of syncope had an underlying pulmonary embolism (PE). As current guidelines do not strongly emphasize evaluation for PE in the workup of syncope, we hypothesize that there might be a higher rate of 30-day readmission due to untreated venous thromboembolism (VTE). The objective of this study is to measure the 30-day readmission rate due to VTE and identify predictors of 30-day readmission with VTE among syncope patients. We identified patients admitted with syncope with ICD9 diagnoses code 780.2 in the Nationwide Readmission Database (NRD-2013), Healthcare Cost and Utilization Project (HCUP). The 30-day readmission rate was calculated using methods described by HCUP. Logistic-regression was used to identify predictors of 30-day readmission with VTE. Discharge weights provided by HCUP were used to generate national estimates. In 2013, NRD included 207,339 eligible patients admitted with syncope. The prevalence rates of PE and DVT were 1.1% and 1.4%, respectively. At least one syncope associated condition was present in 60.9% of the patients. Among the patients who were not diagnosed with VTE during index admission for syncope (N = 188,015), 30-day readmission rate with VTE was 0.5% (0.2% with PE and 0.4% with DVT). In conclusion, low prevalence of VTE in patients with syncope and extremely low 30-day readmission rate with VTE argues against missed diagnoses of VTE in index admission for syncope. These results warrant further studies to determine clinical impact of work up for PE in syncope patients without risk factors.

4568 Background: Advanced sRCC is an aggressive disease with limited responsiveness to chemotherapy and VEGF-targeted therapies. Subgroup analyses from randomized trials showed improved outcomes with ICI, though sample sizes were relatively small. Methods: We conducted a multi-institutional retrospective analysis of consecutive patients (pts) who had RCC with any sarcomatoid component and received systemic therapy for advanced disease. The pts were classified into ICI+ and ICI- groups (gp) based on whether they had received ICI in any treatment line. Overall survival (OS) was measured from the initiation of first systemic therapy. Time to ICI failure (TIF) was defined as the interval from initiation of ICI to subsequent therapy or death. Survival distributions were estimated using the Kaplan-Meier method. Association between covariates and survival was analyzed using multivariate Cox regression. Two-tailed P < 0.05 was considered statistically significant. Results: 203 pts from 6 US academic cancer centers met the inclusion criteria – 155 in ICI+ gp and 48 in ICI- gp. Overall, 137 (67%) pts were male and 181 (89%) were white; median age at mRCC diagnosis was 59.7 (IQR 52.4-67.7) years; 129 (63%) pts presented de novo with distant metastases, 154 (76%) had clear cell (CC) histology, and 182 (90%) had intermediate/poor risk by IMDC criteria. ICI+ had a higher proportion of purely CC tumors (81% vs 64%, P =.02); other demographic and clinical features were similar between the two gps. After a median follow-up of 48.1 (95% CI 40.7-55.5) months (mos), median OS and response rates were significantly higher in the ICI+ gp (Table). OS benefit, compared to ICI-, was maintained in pts who received ICI in ≥ second line (39.6 vs 7.6 mos, HR 0.33, 95% CI 0.22-0.51, log-rank P - (HR 2.50, 95% CI 1.61-3.88, P + had higher OS (18.0 vs 5.5 mos, HR 0.20, 95% CI 0.09-0.44, P -. Conclusions: Treatment with ICI led to markedly higher survival and response rates in advanced sRCC. OS benefit was maintained with ICI in the second line and beyond. Significant benefit was also noted among pts with non-CC or mixed histology sRCC.[Table: see text]

e17012 Background: Salvage therapy for advanced Testicular Carcinoma involves patients receiving ifosfamide are treated in hospital for risk of neuro-toxicities. We evaluated annual trends to assess the health care burden of testicular patients admitted for chemotherapy, as well as co-morbidities and complications associated with mortality. Methods: The National Inpatient Sample is a nationwide sample of all US hospital discharges. We collected data from the years of 2002 to 2017 on patients with Testicular Carcinoma who were receiving chemotherapy, to capture patients recieving ifosfamide and cisplatin in an in-patient setting. Patients undergoing an autologous stem cell transplant were excluded. Annual trends for inpatient mortality, length of stay, and total costs of admission were assessed. A univariate logistic regression analysis was used to calculate odds ratios (OR) for the effect of comorbid conditions and acute inpatient complications on in-patient mortality. Results: Hospitalizations for ifosfamide and cisplatin based treatment among patients with Testicular Carcinoma remained stable from a weighted national estimate of 2,261 in 2002 to 2,160 in 2017. Length of stay increased from 4.6 days to 5.5 days (p=0.01). Cost of stay increased from $26,140 to $53,193 (p

2534 Background: CART-PSMA-TGFβRDN cells are autologous T cells engineered via lentiviral transduction to express a dominant negative form of TGFβRII (TGFβRDN) and a chimeric antigen receptor (CAR) with specificity to prostate specific membrane antigen (PSMA). The TGFβRDN renders CAR T cells resistant to TGFβ-mediated immunosuppression. CART-PSMA-02 is a multi-center, open-label, Phase 1 study evaluating the safety and feasibility of dosing patients with metastatic castration resistant prostate cancer (mCRPC) with CART-PSMA-TGFβRDN (NCT04227275). Methods: This is a 3+3 dose escalation study to determine the recommended phase 2 dose and schedule of CART-PSMA-TGFβRDN cells following lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Single and fractionated doses are being evaluated. A cohort expansion will enroll patients to further explore the safety of the selected dose and schedule. Results: As of January 2021, 6 patients (pts) have been treated. Two pts were treated in the first dose level (1-3 x107 transduced T cells (TDN)). Four pts were treated in the second dose level (1-3 x 108 TDN with fractionated dosing). AEs occurring in ≥50 % of pts included cytokine release syndrome (CRS), anemia, thrombocytopenia, increased creatinine, nausea, fatigue, pyrexia and dehydration. No DLTs occurred in the 1st dose level. Four pts in the 2nd dose level developed CRS (3 Gr 1 and 1 Gr 2). One pt developed rapid G2 CRS that progressed to Gr 5 encephalopathy and Gr 5 multi-organ failure. Ferritin levels peaked at 56,974 ng/ml (baseline 2,903 ng/mL) despite aggressive immunosuppressive therapy including tocilizumab, dexamtheasone and anakinra. The post infusion cytokine profile indicated elevations in IL-1RA, TNF-alpha, VEGF, IL-10, MIP-1b, IFN-gamma, GM-CSF and notably lower levels of IL6 compared to published reports of CD19 CART-mediated CRS. Autopsy findings were consistent with HLH/MAS, confirming overactivity of the monocyte/macrophage compartment. Based on these observations, a modified immune toxicity management strategy that includes prophylactic anakinra (an IL1R antagonist) was instituted. Preliminary evidence of clinical activity of CART-PSMA-TGFβRDN was noted in the 2nd dose level. Two of 3 pts with 1 month follow-up demonstrated PSA decreases from baseline (1 with >95% decrease, 1 with >50% decrease). Both pts had stable disease per RECIST v1.1. A third pt with only 1 week follow-up had a 40% PSA decrease. Additional data analyses from all infused patients are ongoing and data from pts managed with modified immune toxicity management will be presented. Conclusions: Initial data indicates a unique immune toxicity profile and the potential for anti-tumor activity in mCRPC pts treated with CART-PSMA-TGFβRDN. Modified immune toxicity management could lead to identification of a manageable safety profile and therapeutically active dose. Clinical trial information: NCT04227275.

e17020 Background: Radium-223 is an α-emitting radioisotope that induces DNA double-stranded breaks leading to cell death and has improved survival in mCRPC. In preclinical models, PARP inhibitors have shown efficacy as radiosensitizing agents. We designed a phase 1/2 trial to test the hypothesis that radium-223 + olaparib will demonstrate anti-tumor activity in mCRPC irrespective of homologous recombination repair deficiency (HRD) status. Methods: This is an open label, multi-center, phase 1/2 study (NCT03317392) evaluating the dosing, safety and efficacy of radium-223 + olaparib. Eligible patients (pts) had mCRPC with ≥2 bone metastases without visceral metastases or lymphadenopathy > 4 cm. There was no limit on prior therapy. All pts had a baseline biopsy. The phase 1 used a 3+3 dose escalation design with fixed dose radium-223 (55 kBq/kg IV every 4 weeks x 6). Dose level 1 (DL1) was olaparib 200 mg PO BID; DL2 was olaparib 300 mg PO BID. The primary objective was to determine the recommended phase 2 dose (RP2D) and safety. The dose limiting toxicities (DLT) evaluation period was 2 cycles (1 cycle=28 days). Secondary endpoints included radiographic progression-free survival (rPFS) defined by PCWG3 criteria, PSA response (50% decline from baseline), and alkaline phosphatase response (30% decline from baseline). Results: 12 pts were enrolled on the phase 1. Median age was 68 (range 59-81) years. Median prior lines of CRPC therapies was 2 (1-5), including 3 (25%) who had received prior chemotherapy and 100% a prior novel hormone therapy. 6 pts were enrolled at DL1. 1 patient experienced a DLT outside the DLT evaluation period. 3 pts had grade (G) 3-4 treatment-related adverse events (TrAE) including G3 anemia (n=2) and G3 thrombocytopenia (n=1). No patient underwent dose reductions at DL1. 6 pts were enrolled at DL2. 1 patient experienced a DLT outside the DLT evaluation period. 2 pts had G3-4 TrAE including G3 anemia and G4 lymphocytopenia (n=1) and G3 stroke (n=1). 5 underwent dose reductions at DL2. There were no G5 events. Reason for treatment discontinuation is in the table below. After review of safety data, the safety monitoring committee deemed the RP2D of olaparib at 200 mg BID when combined with radium-223. Overall, PSA response and alkaline phosphatase response were 16.7% (n=2, 1 at DL1, 1 at DL2) and 67% (n=8, 3 at DL1, 5 at DL2), respectively. Median follow-up was 6.5 (range 2.8, 11.8) months, and 6-month rPFS was 57% (95% CI: 25%, 80%). Conclusions: We demonstrate that olaparib can be safety combined with radium-223 with RP2 dose of 200 mg BID. The phase 2 study of radium-223 +/- olaparib is accruing (target 120 pts). Outcomes by HRD status will be presented. Clinical trial information: NCT03317392. [Table: see text]

4507 Background: Cisplatin with gemcitabine (CG) remains the standard upfront chemotherapy regimen for metastatic urothelial cancer (mUC). Preclinical synergy was noted between cisplatin and berzosertib, a selective ATR inhibitor. The current study sought to determine if the combination of berzosertib and CG could improve clinical outcomes in mUC. Methods: An open-label, randomized study was conducted across 23 centers in the United States through the Experimental Therapeutics Clinical Trials Network of the National Cancer Institute. Key eligibility criteria included confirmed mUC, no prior cytotoxic therapy for metastatic disease, ≥ 12 months since perioperative therapy and eligibility for cisplatin based on standard criteria. Patients (pts) were randomized to receive either CG alone (control arm) or CG plus berzosertib (experimental arm). In the control arm, 70 mg/m2 of cisplatin was given on day 1 and gemcitabine at 1000 mg/m2 on days 1 and 8 of a 21-day cycle. In the experimental arm, 60 mg/m2 of cisplatin was given on day 1, gemcitabine at 875 mg/m2 on days 1 and 8 and berzosertib at 90 mg/m2 on days 2 and 9 of a 21-day cycle. The primary endpoint of the study was progression-free survival (PFS), with secondary endpoints including response rate (RR), overall survival (OS) and toxicity. Results: A total of 87 pts (median age 67; M:F 68:19) were randomized; 41 pts received CG alone while 46 received CG with berzosertib. Visceral metastases were present in 49% of pts and 52%, 45% and 3% of pts were Bajorin risk 0, 1 and 2, respectively. Median PFS was 8.0 months for both arms (Bajorin risk adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 0.72-2.08). RR was 54%(4 CR, 21 PR) in the CG with berzosertib arm and 63% (4 CR, 22 PR) in CG alone arm (P = 0.66). Median OS was shorter with CG with berzosertib as compared to CG alone (14.4 versus 19.8 months; Bajorin risk adjusted HR 1.42, 95%CI 0.76-2.68). Notably higher rates of grade 3/4 thrombocytopenia (59% vs 39%) and neutropenia (37% vs 27%) were observed with CG plus berzosertib compared to CG alone. Higher rates of toxicity-related discontinuation were seen in the experimental arm (24% vs 15%), and the median cumulative cisplatin dose in the experimental arm was 250 mg/m2, as compared to 370 mg/m2 in the control arm (P < 0.001). Conclusions: No improvement in PFS was observed with the addition of berzosertib to CG, and a trend towards inferior survival was observed. These results suggest caution in reducing the starting dose of cytotoxic therapy to accommodate addition of a myelosuppressive agent, as in the experimental arm of this study. Clinical trial information: NCT02567409.

Medically underserved areas (MUA) or health professional shortage areas (HPSA) designations are based on primary care health services availability. These designations are used in recruiting international medical graduates (IMGs) trained in primary care or subspecialty (e.g., oncology) to areas of need. Whether the MUA/HPSA designation correlates with Oncologist Density (OD) and supports IMG oncologists’ recruitment to areas of need is unknown. We evaluated the concordance of OD with the designation of MUAs/HPSAs and evaluated the impact of OD and MUA/HPSA status on overall survival. We conducted a retrospective cohort study of patients diagnosed with hematological malignancies or metastatic solid tumors in 2011 from the Surveillance Epidemiology and End Results (SEER) database. SEER was linked to the American Medical Association Masterfile to calculate OD, defined as the number of oncologists per 100,000 population at the county level. We calculated the proportion of counties with MUA or HPSA designation for each OD category. Overall survival was estimated using the Kaplan-Meier method and compared between the OD category using a log-rank test. We identified 68,699 adult patients with hematologic malignancies or metastatic solid cancers in 609 counties. The proportion of MUA/HPSA designation was similar across counties categorized by OD (93.2%, 95.4%, 90.3%, and 91.7% in counties with 8.4 oncologists per 100K population, p = 0.7). Patients’ median survival in counties with the lowest OD was significantly lower compared to counties with the highest OD (8 vs. 11 months, p

TPS182 Background: Radium-223 is an α-emitting radioisotope that induces DNA double-stranded breaks leading to cell death and has demonstrated improvement in overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. PARP inhibitors, including olaparib and rucaparib, inhibit repair of DNA single-stranded beaks and have demonstrated clinical efficacy in mCRPC patients harboring alterations in the homologous recombination repair (HRR) pathway. In extensive preclinical cancer models, PARP inhibitors have shown efficacy as radiosensitizing agents. We designed a phase 1/2 trial to test the clinical hypothesis that the combination of radium-223 with olaparib will demonstrate anti-tumor activity in patients with mCRPC irrespective of underlying HRR deficiency status. Methods: This is an open label, multi-center, phase 1/2 study (NCT03317392) evaluating the dosing, safety and efficacy of olaparib in combination with radium-223 in men with mCRPC with bone metastases. Patient must have 2 or more bone metastases and at least 1 bone metastasis that has not been treated with prior radiation therapy. Key exclusion criteria include the presence of visceral metastases or malignant lymphadenopathy exceeding 4 cm and prior therapy with radium-223 and/or PARP inhibitors. The phase 1 component of the study uses a 3+3 dose escalation design to determine the recommended phase 2 dose of olaparib in combination with standard of care dosing of Radium-223. The primary endpoint of the phase 1 component is safety. The phase 2 component of the study is an open-label, randomized study evaluating the combination of olaparib and radium-223 compared to radium-223 alone. The primary endpoint of the phase 2 component is radiographic progression-free survival as defined by Prostate Cancer Working Group 3 guidelines for bone metastases and RECIST v1.1 for non-bone metastases. Secondary endpoints include time to PSA progression, PSA response, time to subsequent therapy, time to first skeletal event, overall survival, and safety. Exploratory endpoints include stratification of response based on HRR alterations, whole exome sequencing of plasma cell free DNA both at baseline, on treatment, and at progression, and evaluation of changes in the tumor immune microenvironment with therapy. As of October 1, 2020, the phase 1 component has completed accrual and we anticipate opening the phase 2 component by December 2020. Clinical trial information: NCT03317392.

e17108 Background: ICI therapy has become the standard of care for many advanced GU cancers, but immune-related adverse events (IRAE) may result in treatment delays or discontinuation. Concurrent vaccine use has been posited to increase the IRAE risk, but safety data is mixed. There are no published data regarding safety of concurrent inactivated vaccines other than influenza, including and especially in the GU cancer population. Methods: We performed a single-institution, retrospective, matched-cohort (1:2, cohort A:B, vaccinated to control) study of all GU cancer patients treated with an inactivated vaccine 30 days prior to or 60 days following ICI therapy from 2015-2019. Baseline clinical characteristics were abstracted from the electronic health record (EHR). Clinically significant IRAEs were defined as any event developing during or 30 days following ICI therapy requiring therapy with ≥ Prednisone 20 mg daily (or equivalent) or other immunosuppression. Delays were defined as ICI therapy given > 14 days past expected date for cycle 2 or beyond. Bivariate analysis with chi-squared statistics were used to describe incidence. Results: Sixty patients were included: 20 in cohort A (vaccinated) and 40 in cohort B (control). Thirty-seven (61.7%) patients had renal cell carcinoma, 17 (31.7%) had urothelial carcinoma, and 4 (6.7%) had prostate cancer. There was no difference in incidence of clinically significant IRAEs between cohorts A and B (15% vs 32.5%, p = 0.148), nor were differences observed in rates of treatment delays (10% vs 12.5%, p = 0.776) or discontinuation (10% vs 12.5%, p = 0.776) due to IRAEs. Most common vaccines were inactivated influenza (n = 18, 90%) and pneumococcal vaccine (n = 3, 15%). Among the 16 patients experiencing clinically-significant IRAEs, the most common were colitis (n = 3), dermatitis (n = 3), and pneumonitis (n = 3). All patients requiring immunosuppressive therapy received systemic corticosteroids. Conclusions: This retrospective cohort study demonstrates that GU cancer patients receiving inactivated vaccines during ICI therapy does not increase IRAE incidence, treatment delays, or discontinuation, suggesting that inactivated vaccines may be safely administered during ICI therapy in this population. Though influenza vaccines were still the most common, this is the first study to include other inactivated vaccines. Limitations include sample size, EHR accuracy and use of surrogate markers for determination of IRAE incidence. Next steps will include a multi-institutional retrospective study.

e17046 Background: Patients receiving neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (MIBC) often are not able to complete three or four cycles of therapy which is standard of care. Pathological completed response (pCR) is a surrogate marker for long term survival. We set out to determine if pCR differed based on total tolerated cycles prior to surgery in those receiving cisplatin based NAC. Methods: Data was gathered at our institution on patients receiving neoadjuvant gemcitabine with cisplatin (GC), or dose dense methotrexate, vinblastin, adriamycin, cisplatin (ddMVAC)). The primary outcome was pCR, and secondary outcome was downstaging. pCR was compared between those who received 1-2, 3, and 4 cycles. Results: A total of 92 patients receiving NAC during the years of 2014 to 2019. 12 received 2 or less cycles, 22 received 3, and 57 completed 4. Age was not significantly different between groups (69.7, ≤ 2), (69.0, 3), (67.4, 4). Gender differences were noted: (41.7% female, ≤ 2), (22.7% female, 3), (12.3% female, 4), p = 0.05. The rates of pCr among the three groups were: (16.7%, ≤ 2), (22.7%, 3), (40.4%, 4), p = 0.14. Downstaging was seen in: (33.3%, ≤ 2), (59.1%, 3), (52.6%, 4), p = 0.35. Conclusions: While not statistically significant our study suggests a trend on pCR rates related to the total of cycles of neoadjuvant chemotherapy prior to surgery. Limitations include retrospective design and small sample size.

This article summarizes the role of adjuvant chemotherapy in muscle-invasive and transitional cell carcinoma of the bladder and upper urinary tract.

4502 Background: Patients with no evidence of disease (NED) after metastasectomy for metastatic renal cell carcinoma (mRCC) are at high risk of recurrence, but no systemic therapy has been shown to benefit this population. Pazopanib is an inhibitor of VEGFR and other kinases that improves progression-free survival in patients with measurable RCC metastatic disease. We performed a randomized, double-blind, placebo-controlled multicenter study to test the hypothesis that pazopanib would improve disease-free survival in patients with mRCC rendered NED after metastasectomy Methods: Patients with NED following metastasectomy were randomized 1:1 to receive pazopanib starting at 800 mg daily vs. placebo for 52 weeks. Patients were stratified by 1 vs. > 1 site of resected disease, and by disease-free interval ≤ vs. > 1 year. Clinical assessment for toxicity and patient-reported outcomes were performed every 4 weeks, and restaging scans every 12 weeks. The study was designed to observe a 42% improvement in disease-free survival (DFS) from 25% to 45% at 3 years. Results: From August 2012 to July 2017, 129 patients were enrolled. The study was unblinded after 83 DFS events had been observed (92% information). The median follow-up from randomization was 30 months (range 0.4 – 66.5 months). The study did not meet the primary endpoint: hazard ratio (95% CI) for DFS was 0.85 (0.55, 1.31) p= 0.47 in favor of pazopanib. At the time of unblinding, 22/129 (17%) of subjects had died. The HR for overall survival (OS) was 2.65 (1.02, 6.9) in favor of placebo ( p= 0.05). Patient-reported outcomes and laboratory correlates will be reported separately. Conclusions: 52 weeks of pazopanib did not improve DFS compared to blinded placebo in patients with mRCC who were NED after metastasectomy. There was a trend toward worse overall survival with pazopanib. Clinical trial information: NCT01575548.

e16547 Background: African American (AA) patients with metastatic castrate-resistant prostate cancer (mCRPC) represent a high-risk population with higher mortality. Recent data suggested that abiraterone acetate (AbA) is more effective in AA in comparison to white patients. There are limited data regarding enzalutamide (Enz) use in AAs. Here, we report the outcomes of (AbA) and (Enz) in AA patients with mCRPC at our center. Methods: A retrospective chart review included AA patients who had a diagnosis of mCRPC and were prescribed AbA and/or Enz at KUMC from 09-01-2008 through 09-01-2018. Patients were divided into two groups: those who started with AbA (abiraterone group) and those who started with Enz (enzalutamide group). Baseline characteristics were compared between the two groups using Fisher’s exact test for categorical variables and the Wilcoxon rank-sum test for continuous variables. The primary outcome was progression-free survival (PFS) on AbA and Enz. PFS was measured from the time of starting either of the two medications to the time of formal relapse, defined by relapse that required therapy change or prostate-cancer-related death. A stepwise Cox proportional-hazard model was used to adjust for potential confounders. Results: During the study period, 28 AA patients with mCRPC received AbA and/or Enz. Twenty-two patients received AbA first, while six patients received Enz first. There were no significant differences in the baseline characteristics between the two groups. Median PFS for the abiraterone group was 24.3 months, while it was 11.7 months for the enzalutamide group, Log-rank test p-value 0.04). After adjusting for potential confounders, the hazard ratio of progression remained significant, favoring the abiraterone group, HR: 0.11, p-value 0.009. Median PFS on AbA after progression on previous Enz was 5.7 months, while it was 4.5 months for Enz after progression on previous AbA, p-value 0.2. Conclusions: In this single-center retrospective study, AA patients with mCRPC who were started on AbA rather than Enz had longer PFS. More studies are needed to understand the best sequence of the two medications in this population.

e18246 Background: Testicular tumors are potentially curable by means of high-dose chemotherapy plus hematopoietic stem-cell rescue. This regimen is commonly used as salvage therapy, third-line or later therapy in patients with platinum-refractory disease. The utilization and real-world outcomes and complications of patients with testicular cancer undergoing autologous hematopoietic stem cell transplant (aHSCT) in United States are unknown. Methods: We queried National Inpatient Sample, a large inpatient data set in the United States, from 2005 to 2014 for male patients with testicular cancer or multiple myeloma (control group) receiving aHSCT and compared outcomes between these groups. The primary outcome was in-hospital mortality rate, and the secondary outcomes included in-hospital complications of aHSCT, length of stay and total charges. Outcomes were assessed by means of univariate analysis, multivariate regression and propensity score matched-pair analysis. Results: A total of 391 patients (weighted N = 1,909) with testicular cancer and 4,809 male patients (weighted N = 23,501) with multiple myeloma who underwent aHSCT from 2005 to 2014 were identified. Mean age of patients with testicular cancer was 32.3 years vs 59 years for multiple myeloma patients (p < 0.001) There were no differences in in-hospital mortality rates (1.5% vs 1.4%, p = 0.85) or rates of intubation (2.3% vs 1.6%, p = 0.36), sepsis (7.7% vs 7.5%, p = 0.94), bacteremia (13.5% vs 15.6%, p = 0.42), or stomatitis (43.8% vs 38.8%, p = 0.87) between patients with testicular cancer and multiple myeloma receiving autologous HSCT. However, utilization of total parenteral nutrition was higher in patients with testicular cancer (12.9% vs 4.7%, p < 0.001). There was no difference in length of stay (17.5 vs 17.5 days, p = 0.77) and total charges (121,120$ vs 123,729$, p = 0.74) between two groups. The results were consistent in multivariate and propensity score matched-pair analysis. Conclusions: The in-hospital outcomes of patients with testicular cancer receiving aHSCT appears to be similar to patients with multiple myeloma. However, overall utilization of aHSCT for testicular cancer appears to be low in United States.

561 Background: Pazopanib as single agent and bevacizumab plus interferon were approved for use in metastatic RCC (MRCC) based on their ability to modulate the vasculature and prolong progression free survival. VEGF levels rose unopposed while using VEGF tyrosine kinase inhibitors (TKI) without break. We hypothesized that adding a break as well as bevacizumab which removes VEGF could prolong PFS in MRCC pts. Methods: This phase I trial was conducted in VEGF treatment naïve MRCC pts. This trial utilized a unique regimen of alternating Pazopanib (day 1-28) with bevacizumab (on days 36 and 50) in a 10-week cycle. The study employed a classic 3+3 design for dose escalation (dose levels in table 1). Safety utilized CTCAE version 4.0 and response evaluation was done using RECIST 1.1 criteria. The primary endpoint of this phase I trial was to find the recommended phase 2 dose (RP2D) of this novel regimen. Key secondary endpoints included objective response rate (ORR), safety/ toxicity and pharmacokinetics. Phase I safety committee acknowledged the completion and approved reporting of Phase I portion of this study. Results: This phase I study was conducted at two academic centers. Twenty-five pts were enrolled in the phase I portion. Median age was 64 years and 68% were male patients. The Commonest adverse events (AE) included fatigue (64%), diarrhea (52%), hypertension (48%), nausea (36%), dysgeusia (36%), vomiting (24%) and proteinuria (28%). The commonest grade 3/4 AE of more than 5% frequency included hypertension (20%) and proteinuria (12%). The dose levels 1 and 4 were expanded due to one DLT each and RP2D was established at dose level 4. The ORR was 25% among evaluable pts who completed at least one cycle of therapy (n=20). The median PFS of the ITT cohort (n=25) was 20.9 months. Conclusions: These data demonstrate that this novel regimen could be safely tested in a phase II trial. The safety and efficacy data suggest that this novel regimen could be optimal for MRCC patients with favorable/intermediate risk. Clinical trial information: NCT01684397. [Table: see text]

207 Background: Prostate cancer accounts for approximately 10% of cancer deaths in men worldwide. Clinical trials for metastatic castrate resistant prostate cancer (mCRPC) have established survival benefit with use of abiraterone (ABI) with prednisone or enzalutamide (ENZ). Despite their wide utilization, little is known about patient quality-of-life (QOL) outcomes for these agents. Our study evaluates patient reported QOL while taking ENZ or ABI/prednisone. Methods: 22 mCRPC patients were enrolled in an open label, nonrandomized manner to receive oral ENZ (n=12) or ABI/prednisone (n=6) per oncologist’s discretion. Patients completed multiple QOL validated questionnaires, including EPIC-26, FACT-P, and FACT-COG at baseline, 1,2,3,6,9 and 12 months or until progression/change of therapy. Surveys were scored by treatment group using mean, median, range, and standard deviations. QOL parameters were compared between the two groups with two-sided, two-sample T test and linear mixed models. Results: Surveys discontinued prior to 1 year secondary to disease progression/change of therapy were 58% and 33% for ENZ and ABI, respectively. By month 3, 50% of surveys were returned for ENZ and 33% for ABI. Month-to-month comparisons of QOL parameters including urinary irritation, incontinence, bowel, sexual, hormonal function, and overall well-being showed no significant differences between treatment groups or different rates of change. Perceived Cognitive Impairment was significantly lower for patients on ABI in month 3, yet Perceived Cognitive Ability favored ENZ in months 2 and 3. All other data points for cognition showed no significant differences. Conclusions: Data from FACT-COG shows discordance in perceived Cognitive Impairment and Abilities between ENZ and ABI in months 2-3. Other QOL domains indicated no difference between the two groups. The study was limited by a significant portion of patients with disease progression/change of therapy. For those on therapy, survey compliance remained high. Thus, the use of questionnaires is a feasible means of assessing patient outcomes and can be adapted to larger studies.

4573Background: Aldesleukin (recombinant human interleukin-2, IL-2) has been an FDA-approved treatment for mRCC since 1992 with a 5-10% rate of durable complete response. Hydroxychloroquine (HCQ) i...

5078Background: The DNA immunotherapy, INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12) was assessed for safety, immunogenicity and the effect on PSA kinetics in biochemically recurrent prostate cancer...

6568Background: ASCO has predicted shortage of 2,550 to 4,080 oncologists by 2020, disproportionately higher in underserved areas. The Conrad-30 program was established for international medical gr...

Background High-dose interleukin-2 (HD IL-2) is used in the treatment of metastatic renal cell carcinoma (mRCC) and has an overall response rate (ORR) of 12–20% and a complete response rate (CR) of 8% in unselected populations with predominantly clear cell type renal cell carcinoma. Nearly 10–15% of patients with renal cell carcinoma exhibit sarcomatoid differentiation, a feature which correlates with a median overall survival (OS) of 9 months and overall poor prognosis. We report a single institution experience with 21 patients with mRCC with sarcomatoid features post-nephrectomy who were treated with HD IL-2. Methods Twenty one patients with mRCC with sarcomatoid features post-nephrectomy who underwent therapy with HD IL-2 were identified at the University of Pittsburgh Medical Center from 2004 to 2016. Baseline patient characteristics, HD IL-2 cycles, time to progression, and subsequent therapies were evaluated. OS and progression-free survival (PFS) in the cohort were calculated using the Kaplan-Meier method. Disease characteristics were evaluated for significance using the Fischer′s exact test and Wilcoxon rank sum test. Results Patients were predominantly Caucasian males with a median age of 54 years. A majority, 86% of these patients, had metastatic disease at time of initial presentation, primarily with lung and lymph node involvement. The ORR and CR with HD IL-2 was 10% and 5%, respectively. Initial localized disease presentation is the only variable that was significantly associated with response to HD IL-2 (p = 0.0158). Number of HD IL-2 doses did not correlate with response with a mean of 16.5 and 15.0 total doses in responders and non-responders, respectively (p = 0.53). Median PFS with HD IL-2 was 7.9 months (95% CI, 5.0–21.3). Median OS was 30.5 months (95% CI 13.3–57.66). Within the subset of patients who had progression on IL-2, median OS was 19.4 months (95% CI, 13.3–35.3). In patients who received second-line therapy, median PFS was 7.9 months (95% CI 2.4–10.2). Conclusion In patients with mRCC with sarcomatoid features, use of HD IL-2 was associated with a modest ORR and a higher survival compared to historical controls (patients with mRCC and sarcomatoid features). Thus, HD IL-2 may have a role in treating selected patients with mRCC with sarcomatoid features.