Jaime R Merchan

University of Miami Miller School of Medicine | UM · Department of Medicine

e13738 Background: The incidence of renal cell carcinoma (RCC) is increasing, with an expected 81,610 new cases and 14,390 deaths in 2024. While clinical characteristics in patients with RCC have been well described, studies focusing on minority patients, such as Hispanic and Latino (HL), are limited. The objectives of the current study are to anal...

e14539 Background: This study explores the transformation of 'cold' tumour microenvironments into 'hot' ones in mRCC, focusing on the potential of Oncolytic Viruses (OVs) for personalized immunotherapy. Recognizing the variability in patient responses, the research underscores the necessity for reliable biomarkers. The objective is to examine the c...

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO...

What is this summary about? This summary provides the results of a study of two treatments for cancer, enfortumab vedotin and pembrolizumab, that were studied together against locally advanced or metastatic urothelial cancer (la/mUC), a cancer that occurs most commonly in the bladder. What were the results? In the 45 patients studied, around 16% d...

[This corrects the article DOI: 10.1371/journal.pcbi.1010263.].

e16555 Background: Annually, there are over 400,000 new renal cell carcinoma (RCC) cases and more than 170,000 deaths worldwide. In the US, 80,000 new cases of RCC are diagnosed each year and almost 14,000 deaths. Over the past half-century, RCC has more than doubled in incidence. RCC seems to have a greater incidence among Hispanics, with a nearly...

4505 Background: Despite available therapeutic options, which include carboplatin-based chemotherapy, PD-1/PD-L1 inhibitor monotherapies, and avelumab maintenance, there is an urgent unmet need for effective and durable 1L therapies for cisplatin-ineligible patients (pts) with la/mUC. Both enfortumab vedotin (EV) and pembrolizumab (P) show survival...

4502 Background: In the phase 3 CLEAR trial, L+P showed clinically meaningful and statistically significant benefits in PFS (primary endpoint) and OS, and improved ORR compared with S in 1L aRCC (Motzer NEJM 2021). Here, we report 4-yr follow-up results from the final prespecified OS analysis of CLEAR (data cutoff: 31 Jul 2022). Methods: Treatment-...

e16554 Background: Annually, there are over 400,000 new renal cell carcinoma (RCC) cases and more than 170,000 deaths worldwide. RCC is one of the top ten more prevalent malignancies in the United States, with 76,000 new cases each year and almost 14,000 deaths. Over the past half-century, RCC has more than doubled in incidence. Studies demonstrate...

PNCK, or CAMK1b, is an understudied kinase of the calcium-calmodulin dependent kinase family which recently has been identified as a marker of cancer progression and survival in several large-scale multi-omics studies. The biology of PNCK and its relation to oncogenesis has also begun to be elucidated, with data suggesting various roles in DNA dama...

Background: Annually, there are over 400,000 new cases of renal cell carcinoma (RCC) and more than 170,000 deaths worldwide. RCC is one of the top ten more prevalent malignancies in the United States, with 76,000 new cases each year and almost 14,000 deaths. Over the past half-century, RCC has more than doubled in incidence. RCC seems to have a gre...

Background: The development of novel biotherapies for metastatic colorectal cancer (CRC), a fatal disease when advanced, is an urgent medical need. Oncolytic viruses (OVs) are novel cancer biotherapies, and the oncolytic measles virus (MV) has demonstrated safety and antitumor activity in early clinical studies. Triptolide (TRP), a diterpenoid epox...

Background: The oncolytic vaccinia virus (VV) is a promising biotherapy undergoing clinical development in human cancer, including renal cell carcinoma (RCC). While VV induces potent tumor oncolysis and immunomodulation, clinical experience has shown that OV therapy alone leads to limited benefit. Moreover, OVs and checkpoint inhibitor combinations...

Background: Lenvatinib plus pembrolizumab showed significantly improved progression-free and overall survival outcomes compared with sunitinib in patients with advanced renal cell carcinoma in the CLEAR study (NCT02811861). Here, we used CLEAR data to characterize common adverse reactions (ARs; adverse-event preferred terms grouped in accordance w...

Background: In the primary analysis of the CLEAR study, lenvatinib plus pembrolizumab significantly improved progression-free survival and overall survival versus sunitinib in patients with advanced renal cell carcinoma (data cutoff Aug 28, 2020). We aimed to assess overall survival based on 7 months of additional follow-up. Methods: This is a p...

Background: Few treatment options are available for patients with advanced renal cell carcinoma who have received previous anti-PD-1-based or anti-PD-L1-based immunotherapy. Combining belzutifan, an HIF-2α inhibitor, with cabozantinib, a multitargeted tyrosine-kinase inhibitor of VEGFR, c-MET, and AXL, might provide more antitumoural effects than...

Background Oncolytic virus V937 showed activity and safety with intratumoral administration. This phase 1 study evaluated intravenous V937±pembrolizumab in patients with advanced solid tumors. Methods Patients had advanced non-small cell lung cancer (NSCLC), urothelial cancer, metastatic castration-resistant prostate cancer, or melanoma in part A...

Renal cell carcinoma (RCC) is amongst the ten most prevalent malignancies in the United States, with 76,000 new cases each year and almost 14,000 deaths. Over the past half-century, RCC has more than doubled in incidence. RCC seems to have a greater incidence among Hispanics with a nearly three-fold increase. The epidemiology of RCC has been studie...

Background CD73 is widely expressed on immune cells playing a critical role in immunomodulatory functions including cell adhesion and migration, as a costimulatory molecule for T cells and in production of adenosine. The function of CD73 expressed on B cells has not been fully characterized. Mupadolimab is an anti-human CD73 antibody that activates...

Renal Cell Carcinoma (RCC) is a fatal disease when advanced. While immunotherapy and tyrosine kinase inhibitor-based combinations are associated with improved survival, the majority of patients eventually succumb to disease. Through a comprehensive pan-cancer, pan-kinome analysis of the Cancer Genome Atlas (TCGA), pregnancy upregulated non-ubiquito...

BACKGROUND Cisplatin-based combination chemotherapy remains the standard of care for locally advanced or metastatic urothelial cancer (la/mUC); however, toxicity is substantial, responses are rarely durable, and many la/mUC patients are ineligible. Enfortumab vedotin and pembrolizumab have each shown a survival benefit versus chemotherapy in UC, ar...

Background: While advances in immune and targeted therapies improve outcomes in selected cancers, only a minority of colorectal cancer (CRC) patients benefit from them. Oncolytic viruses (OVs) represent novel cancer biotherapies, and among them, the oncolytic measles virus (MV) has demonstrated safety and antitumor activity in early clinical studie...

Background: The worldwide incidence of Renal Cell Carcinoma (RCC) is increasing. Although new therapies have improved outcomes in advanced RCC, most patients eventually fail treatment and succumb to this devastating disease. Systemic therapy strategies have focused on TKI and immunotherapy, alone or in combination. Triptolide, a diterpenoid epoxide...

PNCK, or CAMK1b, is an understudied kinase of the calcium-calmodulin dependent kinase family which recently has been identified as a marker of cancer progression and survival in several large-scale multi-omics studies. The biology of PNCK and its relation to oncogenesis has also begun to be elucidated, with data suggesting various roles in DNA dama...

4509 Background: Hypoxia-inducible factor 2α (HIF-2α) is a key oncogenic driver in RCC. Antitumor activity of the HIF-2α inhibitor belzutifan has been observed in RCC and is approved for treatment in patients (pts) with VHL disease who require therapy for associated RCC, CNS hemangioblastomas, or pNETs not requiring immediate surgery. Previous data...

4514 Background: In the open-label, randomized, phase 3 CLEAR study, LEN + PEMBRO had significant PFS (primary endpoint) and OS (key secondary endpoint) benefits over SUN among pts with aRCC in the 1L setting (Motzer 2021, NEJM). We evaluated PFS on next-line therapy (“PFS2”) and explored the effect of subsequent anticancer therapy on OS in the LEN...

Renal Cell Carcinoma (RCC) is a uniformly fatal disease when advanced. While immunotherapy and tyrosine kinase inhibitor-based combinations are associated with improved progression-free and overall survival, the majority of patients eventually develop treatment resistance and succumb to progressive, refractory disease. This underscores the urgent n...

Background Mupadolimab (mupa) is a humanized FcγR binding-deficient IgG1 anti-CD73 antibody that has agonistic properties. ¹ CD73 is involved in production of adenosine and in cellular trafficking. Mupa reacts with the majority of circulating B cells leading to activation and expression of differentiation markers CD69, CD138 and CD38, and transform...

Background Oncolytic viruses (OVs) show significant potential for treating tumors alongside immunotherapies. ¹ VV1 is an OV derived from the innocuous vesicular stomatitis virus (VSV). VV1 has been engineered to expresses human interferon (IFN) β and thyroidal sodium iodide symporter (NIS). ² VV1-infected cells produce IFNβ, which protects non-canc...

Notch signaling plays an important role in development and tissue homeostasis. Deregulation of Notch signaling has been implicated in multiple malignancies. Crenigacestat (LY3039478), a potent Notch inhibitor, decreases Notch signaling and its downstream biologic effects. I6F-MC-JJCD was a multicenter, nonrandomized, open-label, Phase 1b study with...

Background: Enfortumab vedotin (EV) is approved to treat metastatic urothelial carcinoma (mUC) following platinum and PD1/L1 inhibitors. Since the outcomes and patterns of therapy of patients following discontinuation of EV are unknown, we conducted a retrospective study to assess this issue. Methods: Data were retrospectively obtained from pati...

4562 Background: The multicenter, open-label, randomized, phase 3 CLEAR study showed that LEN + EVE had a significant PFS benefit (HR 0.65, 95% CI 0.53-0.80, P<0.001) and improved objective response rate (relative risk 1.48, 95% CI 1.26-1.74) vs SUN in the first-line treatment of patients (pts) with advanced RCC. The difference in overall survival...

5063 Background: ATM mutations, one of a family of DNA repair defects prevalent in prostate cancer, have been included in a list of actionable mutations for PARP inhibitor (PARPi) therapeutic trials. Despite preclinical evidence, PARPi have shown minimal clinical activity in ATM mutant prostate cancer (ATMmPCa). The present analysis explores co-occ...

Hypoxia-inducible factor-2α (HIF-2α) is a transcription factor that frequently accumulates in clear cell renal cell carcinoma (ccRCC), resulting in constitutive activation of genes involved in carcinogenesis. Belzutifan (MK-6482, previously known as PT2977) is a potent, selective small molecule inhibitor of HIF-2α. Maximum tolerated dose, safety, p...

472 Background: Enfortumab Vedotin (EV), an antibody-drug conjugate that targets nectin-4, is approved for metastatic urothelial carcinoma (mUC) progressing post-platinum and PD1/L1 inhibitor therapy. Erdafitinib is approved in patients for post-platinum mUC with activating genomic alterations in FGFR2/3, but the activity of EV in this subset is un...

269 Background: In pts with advanced RCC, second-line treatment with LEN + EVE prolonged progression-free survival (PFS) compared with EVE alone. LEN + PEMBRO, also showed preliminary efficacious evidence in a phase 1/2 RCC study. Here, we describe the investigational study results of first-line LEN + PEMBRO or LEN + EVE versus SUN in pts with adva...

273 Background: Clear cell RCC (ccRCC) accounts for ~70% of kidney cancer cases in the US. Several first-line therapies are approved for ccRCC, but few patients respond completely and most progress within 5-11 mo. A key oncogenic driver in RCC is the transcription factor hypoxia-inducible factor 2α (HIF-2α). MK-6482 is a small molecule HIF-2α inhib...

Background Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear. Methods In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy t...

The tumor stroma acts as a barrier that limits the efficacy of systemically administered oncolytic viruses (OV). We previously demonstrated that stromal-selective, retargeted oncolytic measles viruses (MVs) delay in vivo tumor progression. To further characterize the contribution of stromal targeting to MV’s overall in vivo efficacy in an experimen...

Background: Oncolytic viruses (OVs) represent a promising option for treatment of advanced cancers. There are few studies assessing the effects of oncolytic viruses in renal cell carcinoma. Oncolytic measles virus (MV) is a novel viral platform that previously been shown to induce cell fusion and cytotoxicity in a CD46-dependent manner. The goals o...

5048 Background: Enfortumab vedotin (EV) is an antibody drug conjugate recently approved to treat mUC following prior platinum and PD1/L1 inhibitors. The outcomes and patterns of therapy of pts following discontinuation of EV has yet to be studied. We investigated outcomes of pts who completed EV treatment for mUC at multiple institutions in order...

3090 Background: VV1 (Voyager V1) is derived from VSV, an RNA virus with low human seroprevalence, engineered to replicate selectively in and kill human cancer cells. In Part 1 of this study, we demonstrated the safety of intratumoral VV1 and dose-response, using serum IFNβ as a biomarker; we observed viral replication in tumor and concomitant lymp...

5044 Background: Platinum chemotherapy is the standard for patients (pts) with metastatic urothelial carcinoma (mUC) in the first line (1L) setting. PD-1/PD-L1 inhibitors, such as pembrolizumab (P), have shown promising durability in this setting for PD-L1 high patients. Enfortumab vedotin (EV) is an antibody-drug conjugate that delivers the microt...

5025 Background: Adenosine in the tumor microenvironment (TME) is immunosuppressive and may play a role in resistance to immunotherapy. We described an adenosine induced gene expression signature (AS, Fong, Cancer Disc 2020) that correlates with response to therapy with cifo, an adenosine A2A receptor antagonist, as monotherapy or in combination wi...

TPS5092 Background: Cisplatin-based chemotherapy is the standard for first-line (1L) patients (pts) with locally advanced/metastatic urothelial cancer (LA/mUC). PD-1/PD-L1 inhibitors have promising durability of responses but 1L use is restricted to pts ineligible for cisplatin-containing therapy and whose tumors express PD-L1 (CPS ≥10) or pts inel...

441 Background: Platinum chemotherapy is the standard for patients (pts) with metastatic urothelial carcinoma (mUC) in the first line (1L) setting. In cisplatin-ineligible pts, gem/carbo is a standard therapy, but is poorly tolerated with limited durability and survival. PD-1/PD-L1 inhibitors, such as pembrolizumab (P), have shown promising durabil...

611 Background: Hypoxia-inducible factor (HIF)-2α is a transcription factor that is a key oncogenic driver in RCC. MK-6482 is a first-in-class small molecule HIF-2α inhibitor that blocks the heterodimerization of HIF-2α with HIF-1β and induces regression in mouse xenograft RCC models. Methods: Pts with advanced ccRCC who had received at least 1 pri...

129 Background: Adenosine, generated by the ectonucleotidase CD73, mediates immunosuppression within the tumor microenvironment by triggering adenosine 2A receptors (A2AR) on immune cells. Tumor CD73 expression may be prognostic in prostate cancer. We evaluated the clinical activity of adenosine blockade using A2AR antagonist, ciforadenant, with or...

186 Background: Toca 511 (vocimagene amiretrorepvec) is a cancer-selective, retroviral replicating vector encoding yeast cytosine deaminase that converts 5-fluorocytosine (5-FC) into 5-fluorouracil in the tumor microenvironment (TME). In animal models, Toca 511 and 5-FC kill dividing cancer and nearby immunosuppressive cells, leading to antitumor i...

Background Toca 511 (vocimagene amiretrorepvec) is a cancer-selective, gamma-retroviral replicating vector encoding yeast cytosine deaminase, an enzyme that converts 5 fluorocytosine (5-FC) into 5-fluorouracil in the tumor microenvironment. Preclinical models indicated that Toca 511 and 5-FC treatment kills dividing cancer and nearby immunosuppress...

Background Hypoxia-inducible factor (HIF)-2α is a transcription factor that is a key oncogenic driver in renal cell carcinoma (RCC). PT2977 is a potent and selective small molecule HIF-2α inhibitor that prevents HIF-2α from heterodimerizing with HIF-1β, blocking the expression of HIF-2α target genes in tumour cells, and inducing regressions in mous...

Background Platinum-based chemotherapy remains the standard of care for patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC). Despite the use of first-line (1L) PD-1/PD-1L inhibitors, 71–76% of pts who are cisplatin-ineligible do not respond. EV is an antibody-drug conjugate targeting Nectin-4, which is highly expressed...

216 Background: The University of Miami’s Phase I Program is South Florida’s only academic Phase I center dedicated to drug development for cancer patients. On April 2018, Sylvester Comprehensive Cancer Center opened the Phase I/Experimental Therapeutics (ET) Clinic dedicated to research patients enrolled in Phase I clinical trials and established...

Kinases are firmly established drug targets in cancer. There are currently 44 FDA approved kinase drug and hundreds of compounds are in clinical development. However, less than 10% of the Kinome is currently targeted and a large proportion is considered understudied by the NIH Illuminating the Druggable Genome Program (https://druggablegenome.net/)...

Kinases are firmly established drug targets in cancer. There are currently 44 FDA approved kinase drug and hundreds of compounds are in clinical development. However, less than 10% of the Kinome is currently targeted and a large proportion is considered understudied by the NIH Illuminating the Druggable Genome Program (https://druggablegenome.net/)...

TPS2671 Background: RP1 is an attenuated oncolytic HSV-1 that expresses a fusogenic glycoprotein from gibbon ape leukemia virus (GALV-GP R-) and GM-CSF. RP1 induces potent GALV-GP R- enhanced immunogenic cell death and host anti-tumor immunity in murine tumor models and increases PD-L1 expression. This clinical trial (NCT03767348) was designed to t...

TPS2646 Background: CD73 expression is elevated in tumors and contributes to increasing levels of immunosuppressive adenosine in the tumor microenvironment. CD73 knockout mice exhibit reduced tumor growth and resistance to experimental metastasis. Inhibition of CD73 activity with an anti-CD73 antibody blocks adenosine production, shown to inhibit t...

2505 Background: CPI-006 inhibits CD73, a nucelotidase that converts AMP to adenosine and functions as a lymphocyte adhesion molecule. CPI-006 is a humanized IgG1 FcγR binding-deficient antibody that binds to CD73+ T and B lymphocytes leading to activation of B cells and expression of CD69. This study investigates the immunobiology, safety, and eff...

Background VEGF promotes an immunosuppressive microenvironment and contributes to immune checkpoint inhibitor resistance in cancer. We aimed to assess the activity of the VEGF receptor tyrosine-kinase inhibitor axitinib plus the anti-PD-1 immune checkpoint inhibitor pembrolizumab in patients with sarcoma. Methods This single-centre, single-arm, ph...

Background Deregulated Notch signaling is implicated in multiple cancers. The phase I trial (I6F-MC-JJCA) investigated the safety and anti-tumor activity of crenigacestat (LY3039478), a selective oral Notch inhibitor, in an expansion cohort of patients with adenoid cystic carcinoma (ACC) who received the dose-escalation-recommended phase 2 dose (RP...

377 Background: Enfortumab vedotin (EV) is an antibody–drug conjugate that delivers MMAE, a microtubule disrupting agent, to tumors expressing Nectin-4, a protein found on most urothelial cancers. Preliminary results of the EV-101 study (NCT02091999) suggest EV is active and tolerable. Methods: Patients with mUC treated with ≥1 prior chemotherapy,...

558 Background: The transcription factor hypoxia-inducible factor (HIF)-2α has been established as an oncogenic driver in clear cell renal cell carcinoma (ccRCC) due to underlying VHL deficiency. Activation of HIF-2α can also promote immunosuppression. In preclinical models, HIF-2α inhibition demonstrated increased efficacy in combination with chec...

Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector that selectively infects cancer cells due to cell division requirements for virus integration into the genome, and defects in innate and adaptive immune responses found in malignant tissues that support virus replication. Toca 511 spreads...

Background: LY3039478 is an orally bioavailable selective Notch inhibitor. This phase 1a/b trial evaluated the safety, pharmacokinetics and antitumour activity of LY3039478 in patients with soft tissue sarcoma (STS) and gastrointestinal stromal tumour (GIST). Methods: This multipart, phase 1 trial enrolled patients with refractory advanced/metas...

Introduction Voyager-V1TM is derived from VSV, a bullet-shaped negative sense RNA virus with very low human seroprevalence; it is engineered to selectively replicate in and kill human cancer cells. Voyager-V1 encodes the human IFNβ gene to boost antitumoral immune responses and the thyroidal sodium iodide symporter NIS gene to permit noninvasive im...

Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic retroviral replicating vector (RRV) that selectively infects cancer cells. Toca 511 spreads through tumors, stably delivering an optimized cytosine deaminase (CD) gene that converts the prodrug, Toca FC (investigational, extended-release 5-FC), into 5-FU. Based on precl...

Background: Oncolytic viruses offer an advantage over other treatment options, as they both induce cytotoxicity as well as immune modulation. Oncolytic measles virus (MV) is a safe and promising oncolytic viral vector that is being tested in early clinical trials for treatment of cancer. While the oncolytic activity of MV has been clearly defined,...

Efficient systemic delivery of oncolytic viruses remains an unresolved issue and an obstacle to the success of oncolytic virotherapy. One of the main barriers that lead to decreased oncolytic viral delivery to tumor cells is the tumor stromal component. A potential strategy to circumvent this problem is to use a retargeted oncolytic virus that is a...

431 Background: EV is an ADC that selectively targets and kills cells expressing Nectin-4 by delivering a potent microtubule-disrupting agent, monomethyl auristatin E. As mUC tumors express Nectin-4 in almost all pts, the EV clinical profile was assessed in an ongoing Phase 1 study (NCT02091999) at the recommended phase 2 dose (RP2D; 1.25 mg/kg) in...

The phase III MPACT trial for metastatic pancreatic cancer (PC) showed improved overall survival (OS), progression free survival (PFS) and response rates (RRs) for first-line nab-paclitaxel (Abraxane) and gemcitabine (the AG combination) compared to gemcitabine monotherapy. The safety and efficacy of the AG combination has not been systematically s...

TPS880 Background: Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector (RRV). RRVs selectively infect cancer cells due to defects in innate and adaptive immune responses found in cancers that support virus replication, and the requirement for cell division for virus integration into the gen...

396 Background: RX-3117 is an oral small-molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 2 of the Phase 1b/2a clinical study of RX3117 as a single agent in subje...

Toca 511, a clinical-stage retroviral replicating vector (RRV) encoding an optimized yeast cytosine deaminase (CD) prodrug activator gene, in combination with Toca FC (extended-release 5-fluorocytosine (5-FC)), is designed to produce 5-FU which kills cancer cells and immune-suppressive myeloid cells in the tumor microenvironment, leading to anti-ca...

The tumor microenvironment (TME) is a relevant target for novel biological therapies. MV-m-uPA and MV-h-uPA are fully retargeted, species-specific, oncolytic measles viruses (MV) directed against murine or human urokinase receptor (PLAUR/uPAR), expressed in tumor and stromal cells. The effects of stromal-selective targeting by uPAR-retargeted MVs w...

The tumor microenvironment is a relevant target for novel biological therapies. While it has been demonstrated that tumor-stromal cell interactions are important in the sensitivity of the cancer cells to oncolytic virues, few studies have investigated the direct effects of an oncolytic virus on the stroma, and its implications on the virus antitumo...

e14636Background: The number of new OV CT have been increasing along with the evolution of cancer immunotherapy. The OVs induce direct oncolysis and enhances the host innate and adaptive immunity. There are ongoing efforts to improve the anticancer efficacy of OVs with combinational strategies. However, there has been no direct comparison of OV CTs...

6024 Background: ACCs have high levels of Notch-1 receptor expression and activation. LY3039478 (LY) is an orally bioavailable selective Notch inhibitor (Notch 1-4). Here we report on safety, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of LY in patients (pts) with ACC. Methods: Ongoing, multi-part, phase I trial enrolled p...

106 Background: Enfortumab vedotin, an antibody–drug conjugate, delivers monomethyl auristatin E to tumors expressing Nectin-4, which is overexpressed in metastatic urothelial cancer (mUC). Methods: This Phase I study (NCT02091999) enrolled patients (pts) with solid tumors, including pts with mUC, treated with ≥1 prior chemotherapy regimen. All pts...

445 Background: RX-3117 is an oral smallmolecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 1 of the Phase 1b/2a clinical study of RX3117 as a single agent in subjec...

Purpose: To describe safety and effectiveness of percutaneous irreversible electroporation (IRE) for treatment of unresectable, locally advanced pancreatic adenocarcinoma (LAPC). Materials and methods: This retrospective study included 50 patients (23 women, 27 men; age range, 46-91 y; median age, 62.5 y) with biopsy-proven, unresectable LAPC wh...