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507 Background: There is no established neoadjuvant therapy (NAT) for patients (pt) with muscle invasive bladder cancer (MIBC) ineligible for cisplatin-based chemotherapy preceding radical cystectomy. Encouraging prospective data indicate PD-1/PD-L1 inhibitors, including pembrolizumab and atezolizumab, are safe and active as NAT for MIBC. Durvalumab (D), a PD-L1 inhibitor, is FDA approved for treating locally advanced or metastatic urothelial carcinoma following platinum-based chemotherapy. The safety and activity of D as NAT in MIBC have not been reported. Methods: We are conducting a single-center sequential multicohort trial (NCT03773666) of D alone (Cohort 1, N=10) and D plus the CD73 inhibitor oleclumab (Cohort 2, N=10) in cT2-T4aN0M0 MIBC pts who are RC candidates and are ineligible for or declined cisplatin-based chemotherapy. The primary endpoint is feasibility, defined as ≥7 of 10 pts receiving at least 1 dose of D followed by radical cystectomy without dose limiting toxicity (DLT) up to 12 wks post-RC. In Cohort 1, D is administered at 750mg IV Q2W for 3 cycles followed by RC 2-4 weeks after the last dose. Baseline and RC tissue and baseline and on-study blood are collected for correlative studies, including immunohistochemistry, genomics, transcriptomics, and metabolomics. Results: Cohort 1 has completed enrollment; ten pts were enrolled between Feb 2019 to Sept 2019. Median age was 67 (Range: 53-85) and 8 (80%) were men. All 10 pts completed 3 durvalumab doses. Eight pts completed planned RC with at least 12wk follow-up post-op to date. No DLTs were observed. One Grade 3 treatment-related adverse event (trAE) was reported (anemia), with no Grade 4 or higher trAE. Pathologic response (

740 Background: Metastatic vRCC are aggressive tumors with poor prognosis. Our phase 2 trial of AB in vRCC showed a response rate of 33%. We investigated on-therapy changes in circulating immune cells and cytokines and their association with outcomes. Methods: Blood was collected at baseline (C1D1) and on-therapy (C3D1). Peripheral blood mononuclear cells were analyzed for cell type, expression of immune checkpoints, markers of activation, proliferation and function using flow cytometry; circulating cytokines by multiplex immunoassay. Relationship with progression-free (PFS) and overall survival (OS) was assessed by cox regression models. Results: Baseline and on-therapy samples were collected from all 60 patients. High baseline levels of immunosuppressive cytokines IL1α, IL6, CCL4 and IL13, as well as high baseline levels of CD4+ lymphocytes expressing CD69, were associated with inferior PFS and OS (Table). However, a decline in these markers on-therapy was not predictive of outcomes. On-therapy assessments showed an increase in the IFN-γ inducible cytokine CXCL10 (p

2006Background: Blockade of programmed-death 1 (PD-1) mediated immunosuppression has achieved meaningful benefit across many cancers. Vascular endothelial growth factor (VEGF), a highly upregulated...

2037Background: The neurologic assessment in neuro-oncology (NANO) scale was developed as a standardized metric to objectively measure neurologic function in patients (pts) with brain tumors to com...

TPS1126 Background: Stage 2-3 triple negative breast cancer (TNBC) remains at high risk for recurrence despite modern adjuvant therapy. An important role for the immune system in TNBC has recently emerged. Tumor infiltrating lymphocytes (TILs) are correlated with improved prognosis and several PD-1/PD-L1 checkpoint inhibitors, including Durvalumab (DUR), demonstrated activity in metastatic TNBC. Vaccines are a promising approach to further enhance the immune response in many cancers including TNBC. PVX-410 (PVX) is a novel tetra-peptide vaccine against XBP1 (2 splice variants), CD138 and CS1 that was safe and induced immune responses in a phase 1b study in smoldering myeloma. XBP1 and CD138 are also over-expressed in TNBC. Methods: This Phase 1b multi-center, single arm study will enroll 20 HLA-A2+ female patients (pts) following completion of all adjuvant therapy for stage 2-3 TNBC. Pts will receive 6 doses of 800ug PVX (emulsified in Montanide (SC) and co-administered with Hiltonol (IM)) at 2-week intervals, and 2 doses of DUR 1500mg IV at the 4th and 6th vaccine visits. Eligible pts must be between 1-6 months from completing adjuvant therapy, have no prior autoimmune disease, and have residual disease if neoadjuvant therapy was used. The primary objective is to determine the safety and tolerability of the combination, and the key secondary objective is to determine the immune response to PVX + DUR. If ≤1 pt in the first 6 has a protocol defined dose limiting toxicity within 4 weeks after the first DUR dose, accrual will continue to 20 pts. Immune response will be assessed at baseline, pre-dose 4 PVX/dose 1 DUR, and 4 weeks after completing protocol therapy. Paired data in 20 pts provides 90% power to see a shift of 0.75 standardized units from baseline to 4 weeks post treatment with the signed rank test. Immune response will be determined by a FACs based assay of antigen specific CD3+CD8+ T lymphocyte response and IFN-γ production (intracellular staining) in patient PBMCs. Additional correlative studies, including T-cell PD-1 and tissue PD-L1, XBP1, and CD138, are planned. Currently 4 pts are enrolled. Clinical trial information: NCT02826434.