Alcoholic Liver Disease- blood draw only

This study is to investigate the predisposition of human subjects to advanced alcoholic steatohepatitis due to hepatic deficiency or anomaly in a protein named augmenter of liver regeneration (ALR). Cirrhotic and non-cirrhotic patients with a history of heavy alcohol use or abuse are being compared. A one time blood draw is all that is involved.

Biomarkers in Neurodegenerative Diseases

Viewing Parkinson disease (PD), Alzheimer’s disease (AD), as well as other neurodegenerative diseases, as single entities has been useful to develop treatments for symptoms dependent on common denominators, such as deficiencies in dopamine or in acetylcholine. The development of disease modifying therapies, on the other hand, will require a “precision medicine” approach, aiming at classifying individual patients into distinctive molecular subtypes. Each of these subtypes is expected to respond differentially to any of a range of treatments. In this study, eligible patients who have been diagnosed with neurodegenerative disorders as well as healthy controls will be followed annually after a comprehensive baseline examination. Samples of DNA, RNA, peripheral blood mononuclear cells (PBMCs), plasma proteins, urine, and gut microbiota will be collected and stored for future analyses. Such data will inform biological subtypes of disease that will enable the repurposing of therapies targeted to those with the appropriate biology in order to slow their disease progression (precision medicine). Patient population: 4000 patients diagnosed with PD and PD-like diseases as well as AD and AD-like diseases will be invited to participate as study subjects. 1000 healthy control patients will also be invited to participate. Referrals from other Cincinnati-area neurologists will also be accepted. One-thousand healthy controls will be recruited through specific advertisement campaigns and relatives of participating patients.

Evaluation of Cendakimab for EoE

Double-blind, randomized, placebo controlled induction and maintenance study to evaluate safety and efficacy of cendakimab (CC-93538) in adults. CC-93538 is a recombinant humanized, high-affinity neutralizing IgG1κ monoclonal antibody selective for interleukin-13 (IL-13). CC-93538 binds to IL-13, preventing its interaction with both IL-13 receptors. Subjects will be randomized 1:1:1 to the following treatment arms for the 24-week Induction and 24-week Maintenance Phases: - CC-93538 360 mg SC once weekly for 24 weeks followed by CC-93538 360 mg SC once weekly for 24 weeks - CC-93538 360 mg SC once weekly for 24 weeks followed by CC-93538 360 mg SC once every other week for 24 weeks. - Matching placebo SC once weekly for 24 weeks followed by matching placebo SC once weekly for 24 weeks The CC-93538 360 mg SC dose will be administered by 2 injections of 1.2 mL each provided in 150 mg/mL pre-filled syringes. Matching placebo will also be administered as 2 injections of 1.2 mL. Dysphagia is monitored via daily e-diary questionnaire completion. Study visits occur approximately every 4 weeks. EGD with biopsies at screening, W24, and W48.

PK Study on SOC Carboplatin

This is a PK study for any patient who is going to be receiving Carboplatin as part of their standard of care treatment. Patients will receive 5.0 mL bolus dose of iohexol, followed by a saline flush via IV when they first come into the clinic. Patients will then be assessed for hypersensitivity reactions for a minimum of 20 minutes before they proceed with their regular carboplatin treatment regimen. PK draws will be up to 6 hours after iohexol dose.

This study may be approprate for those with:Relapsed/Recurrent Cancer

CRC- Metastatic, newly diagnosed

The study will assess the safety and efficacy of BXQ-350 plus modified FOLFOX7 (mFOLFOX7) and bevacizumab in participants who have newly diagnosed metastatic adenocarcinoma of the colon/rectum. The study will also evaluate if the administration of BXQ-350 with mFOLFOX7 and bevacizumab may diminish oxaliplatin induced sensory neurotoxicity, enabling participants to receive the total and planned doses of mFOLFOX7. All participants will receive BXQ-350 by intravenous (IV) infusion along with standard of care doses of mFOLFOX and bevacizumab. The study is divided into two stages: Stage 1 will be open label and will enroll participants at increasing dose levels of BXQ-350 in order to determine the Stage 2 dose. Stage 2 will be blinded; participants will receive BXQ-350 at the established Stage 1 dose or placebo BXQ-350 is a novel anti-neoplastic therapeutic agent configured from two components: Saposin C (SapC), an expressed (human) lysosomal protein, and the phospholipid dioleoylphosphatidyl-serine (DOPS), a cell membrane phospholipid (clinical formulation BXQ-350).Due to the presumed mechanism of action of BXQ-350, Bexion anticipates that it may have an impact on ceramides, sphingosine-1-phosphate (S1P), and inflammatory cytokine levels. In addition, pre-clinical results demonstrated that BXQ-350 induced neurite generation and protection in vitro in the PC-12 and NS20Y cell lines and significantly decreased oxaliplatin-induced cold allodynia in a model of CIPN. Thus BXQ-350 may represent a new approach to deliver a neuropathy benefit. The unique combination of BXQ-350 along with its proven safety profile, potential efficacy, and possible neuropathy benefit makes BXQ-350 a worthwhile candidate to use in combination with standard of care treatment for mCRC to not only enhance the standard treatment of mCRC, but also to evaluate its ability to alleviate side effects related to oxaliplatin-induced sensory neurotoxicity.

Beat AML S8, S17, S12 (S14, S18 closed)

This screening and multi-sub-study Phase 1b/2 trial will establish a method for genomic screening followed by assigning and accruing simultaneously to a multi-study "Master Protocol (BAML-16-001-M1)." The specific subtype of acute myeloid leukemia will determine which sub-study, within this protocol, a participant will be assigned to evaluate investigational therapies or combinations with the ultimate goal of advancing new targeted therapies for approval. The study also includes a marker negative sub-study which will include all screened patients not eligible for any of the biomarker-driven sub-studies. *SubProtocol S8 This is an open-label Phase 1b/2 clinical study of gilteritinib monotherapy, gilteritinib in combination with decitabine, or gilteritinib in combination with decitabine and venetoclax in untreated FLT3 mutated AML with high and low variant allele frequency. Initially, the combination of gilteritinib and decitabine was tested (Group 1); however, subsequently the combination of decitabine and venetoclax was shown to be a highly effective therapy for older AML patients, so the triple combination of gilteritinib in combination with decitabine and venetoclax (Group 2) is now being evaluated in this study. *SubProtocol S10 STUDY DISCOUNTINUED BY SPONSOR *SubProtocol S14 The study is an open-label Phase 1b/2 clinical study of TP-0903 given in addition to decitabine in patients ≥ 60 years with newly diagnosed, previously untreated AML with TP53 mutations and/or complex karyotype. The Phase 1b portion of this study will use a standard 3 + 3 design with dose escalation based upon dose limiting toxicities. The maximum tolerated dose will be defined as the highest dose where at most 1 patient in 6 experiences dose-limiting toxicity, and this is generally the recommended Phase 2 dose (RP2D). Once the RP2D is determined from Phase 1b, patients will be enrolled at this dose level to initiate the Phase 2 portion of the study.

Rec. HNSCC- Pembro+Cesium 131 w/ Surgery

Phase 1 of this study that will determine the safety of the combination of pembrolizumab and Cesium-131 in recurrent HNSCC patients undergoing salvage surgical resection. Phase 2 will determine the disease free survival rate of this combination. Patients will receive one 200mg IV dose of pembrolizumab followed by salvage surgery. At the time of surgery, they will have Cesium131 seeds implanted. Two to six weeks after surgery, subjects will be started on 200 mg IV of pembrolizumab to be continued every 3 weeks for 6 months

Advanced Solid Tumors; KRAS-MAPK mutated

A Phase 1/2 Multiple Expansion Cohort Trial of the SOS1 Inhibitor MRTX0902 in Patients with Advanced Solid Tumors Harboring Mutations in the KRAS-MAPK Pathway

Adv. Solid tumors w/ G12C Mut- MRTX849

This is a multi-center, multiple expansion cohort trial evaluating the safety, PK, metabolites, PD and clinical activity/efficacy of MRTX849 in patients with advanced solid tumor malignancies with KRAS G12C mutation. MRTX849 will be given to patients in capsules and taken orally once daily. In phase 1, patients will take MRTX849 in varying doses. In phase 2, once dose level has been determined the study will enroll people with different types of cancer.

BladderCA- ChemoRT+Atezolizumab

This is a randomized study for patients with Urothelial bladder cancer. Patients must have either cisplatin, 5-flurouracil + mitomycin, or gemcitabine chemotherapy planned for their treatment regimen, as decided by the treating physician. Patients will also undergo radiation therapy. Those randomized to Arm 2 of the study will also receive Atezolizumab Q3W for 6 months, in addition to planned chemo and RT. The primary endpoint of this study is to compare bladder intact event-free survival (BI-EFS) for concurrent chemoradiation therapy (CRT) with and without atezolizumab in localized muscle invasive bladder cancer (MIBC)

IDEAYA Biosciences

This is a Phase 1/2, multi-center, open-label basket study designed to evaluate the safety and anti-tumor activity of IDE196 in patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations or PRKC fusions, including metastatic uveal melanoma (MUM), cutaneous melanoma, colorectal cancer, and other solid tumors.Phase 1 (dose escalation - monotherapy) will assess safety, tolerability and pharmacokinetics of IDE196 via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.Phase 1 Tablet and Food Effect Pharmacokinetic (PK) Substudy will assess the PK profile of IDE196 tablet and evaluate the effects of food on the PK profile of IDE196 tabletPhase 1 (dose escalation - binimetib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and binimetinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.Phase 1 (dose escalation - crizotinib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and crizotinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.

FGFR2 muts in cholangio + solid tumors

Fibroblast Growth Factor Receptor 2 (FGFR2) genomic alterations are rare oncogenic drivers that occur across multiple solid tumor indications. Clinical anti-tumor activity observed with pan-FGFR inhibitors (eg. pemigatinib, erdifitinib, infigratinib, TAS-120) has confirmed the oncogenic role of FGFR2 alterations, particularly in intrahepatic cholangiocarcinoma (ICC), the indication with the highest rate of FGFR2-fusions. Clinical activity with pan-FGFR inhibitors has also been observed in patients with other pathway alterations, such as FGFR mRNA overexpression, suggesting a potentially broader role for FGFR2 inhibitors. However, FGFR1-related toxicity (e.g. hyperphosphatemia; tissue mineralization) with pan-FGFR inhibitors limits dosing and Key Inclusion Criteria• Histologically or cytologically confirmed unresectable ICC or other advanced solid tumor• Documented FGFR2 gene fusion, mutation, or amplification per local testing of blood and/or tumor (See protocol for specified eligible alterations)• Disease that is refractory to standard therapy, has not adequately responded to standard therapy, disease for which no standard or curative therapy exists, or the patient must be intolerant to or have declined standard therapy• Measurable or evaluable disease (RECIST v1.1)• ECOG PS 0-2• Part 1 dose escalation patients must have Advanced solid tumor with FGFR genomic alterations• Part 2 dose expansion patients must additionally meet the following group requirements:o Group 1 - ICC with FGFR2 fusion previously treated with a pan-FGFR inhibitoro Group 2 - ICC with FGFR2 fusion NOT previously treated with a pan-FGFR inhibitoro Group 3 - Advanced solid tumor (other than ICC) with FGFR2 fusiono Group 4 - Advanced solid tumor with FGFR2 amplificationo Group 5 - Advanced solid tumor with an oncogenic FGFR2 mutationKey Exclusion Criteria• Presence of a primary driver alteration other than FGFR2 that is amenable to an approved targeted therapy• Ongoing, clinically significant corneal or retinal disorder• QT interval (QTcF) > 480 msec or history of prolonged QT syndrome, Torsades de pointes or familial history of prolonged QT syndrome• Clinically significant, uncontrolled cardiovascular disease• CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms• Local, hepatic therapy (eg. TACE or Y90) within 4 weeksefficacy. RLY-4008 is a highly selective, oral FGFR2 inhibitor, with 80 to > 5000 fold selectivity for FGFR2 relative to FGFR1, FGFR3 and FGFR4 and significant potency against oncogenic FGFR2 alterations and common resistance mutations (eg. gatekeeper mutations). This first-in-human study will define the MTD and RP2D, safety profile, PK, PD and preliminary anti-tumor activity of RLY-4008 in patients with ICC and other advanced solid tumors.

This study may be approprate for those with:New Diagnosed Cancer

cervical cancer, recurrent or stage IVB

The dose escalation part will occur in participants with cervical cancer who have progressed during or after standard of care therapy and who are intolerant or ineligible to receive standard of care treatments. Arm A will be conducted by escalating doses of both tisotumab vedotin and bevacizumab. Dose escalations of the tisotumab vedotin + pembrolizumab and tisotumab vedotin + carboplatin combinations (Arms B and C, respectively) will be conducted by combining fixed doses of either pembrolizumab or carboplatin with increasing doses of tisotumab vedotin. The dose expansion part of this study (Arms D through H) will be conducted in 2 populations: participants with cervical cancer who have not received prior systemic therapy for recurrent or stage IVB cervical cancer (Arms D, E, and H) and participants with cervical cancer who have progressed on or after at least 1 but no more than 2 prior systemic therapies (Arms F and G). Participants enrolled to Arms D, E, F and H will receive the RP2D of tisotumab vedotin established in the dose escalation part. Participants enrolled to Arm G will receive tisotumab vedotin weekly (at a dose lower than subjects in all other Arms) for three weeks and 1 week off (28-day treatment cycle). This is an open label, multi-center trial of The trial consists of two-parts a dose escalation part and an expansion part. The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) of the combinations have been determined in the dose escalation part.

EndometrialCA- Hypofractionated WPRT

This is a Phase I study evaluating the safety of adjuvant hypofractionated whole pelvis radiation therapy (WPRT) in endometrial cancer. The primary objective of the study is to determine the maximum tolerated dose per fraction (MTDF), defined by acceptable acute clinician-reported GI and GU toxicity and patient-reported GI toxicity, of WPRT from among the two study dose levels. Cohort 1 will receive hypofractionated WPRT at 41.25 Gy over 15 fractions and Cohort 2 will receive 38 Gy over 10 fractions.

NSCLC-PD-L1_Met_1st line

This phase III trial studies whether pembrolizumab alone as a first-line treatment, followed by pemetrexed and carboplatin with or without pembrolizumab after disease progression is superior to induction with pembrolizumab, pemetrexed and carboplatin followed by pembrolizumab and pemetrexed maintenance in treating patients with stage IV non-squamous non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as pemetrexed and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving first-line pembrolizumab followed by pemetrexed and carboplatin with or without pembrolizumab works better in treating patients with non-squamous non-small cell cancer.

Protons vs Photon RT in Liver Cancer

Randomized trial for patients with Hepatocellular Carcinoma to either proton or photon radiotherapy. Primary endpoint is to determine if overall survival is different for patients treated with protons compared to photons.

Multiple Myeloma, Newly Diagnosed

This phase III trial compares the combination of four drugs (daratumumab, bortezomib, lenalidomide and dexamethasone) to the use of a three drug combination (daratumumab, lenalidomide and dexamethasone). Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth

Solid tumor; TSC1 or TSC2 alteration

TSC-007 is a prospective Phase 2, open-label, multi-institutional basket trial to determine the efficacy and safety profile of nab-sirolimus administered by intravenous (IV) infusion to patients with malignant solid tumors with pathogenic inactivating TSC1 (Arm A) or TSC2 (Arm B) alterations, each Arm studied independently. A cycle will consist of 21 days. Patients will receive nab-sirolimus by IV infusion over 30 minutes (+10 mins window allowed; ie, 30–40 mins infusion) once weekly for 2 weeks followed by a week of rest (qw2/3). Nab-Sirolimus will be administered at 100 mg/m2. Patients will continue treatment until disease progression, or unacceptable toxicity, or until in the opinion of the investigator the patient is no longer benefiting from therapy, or at patient discretion. In pre-clinical trials, nab-Sirolimus produced a fairly dose proportional increase of Cmax and AUC across the dose range tested, and it significantly inhibited mTOR targets S6K and 4EBP1. This study is currently enrolling in Phase 2.