Project description:Venetoclax with azacitidine is the standard of care for newly diagnosed AML patients who are unfit for intensive induction chemotherapy. CC-486 is the oral formulation of azacitidine that is currently approved for post-induction chemotherapy maintenance in AML. In this single center open label, Phase 1/1b study, we investigated CC-486 and venetoclax in relapsed and refractory AML and newly diagnosed patients. In the dose escalation phase, patients received CC-486 at one of two cohorts (200 mg PO days 1-14 and 300 mg PO days 1-14). Venetoclax was given at the 400 mg/day PO regimen, for 28 days, after an initial intra-patient dose escalation per the standard of care. Using a 3+3 study design for these two cohorts, we determined the recommended dose of CC-486 to be 300mg daily on days 1-14. Most common adverse events included nausea, diarrhea, fatigue and cytopenias. The incidence of grade 3 or greater neutropenia or thrombocytopenia was 97% and 66%, respectively. There were no dose limiting toxicities in either cohort. The expansion phase of the study consisted of 10 additional relapsed and refractory patients and 16 patients with newly diagnosed AML. Responses were seen in all phases of the study, and six patients were successfully bridged to hematopoietic stem cell transplant. Correlative analyses including sequencing and metabolomics performed on patient samples suggested this regimen had a similar effect on leukemia stem cells compared with conventional (intravenous) azacitidine and venetoclax.
Project description:This is a multi-center, open label, repeat dose, Phase 1 study consisting of a Dose Escalation Phase and a Dose Expansion Phase to evaluate safety, pharmacokinetics, and clinical activity.
Project description:A Phase I, Open-Label, Dose-Escalation Study of the OX40 Agonist Ivuxolimab in Patients With Locally Advanced or Metastatic Cancers
Project description:This is a two-part, Phase 1 open label, multi-center, dose escalation study of CEP-37250/KHK2804 as monotherapy in subjects with advanced solid tumors who no longer respond to standard therapy or for whom no standard therapy is available.
Project description:This is a Phase 1/2a, open-label, multi-center study of JAB-3068 in Patients with advanced solid tumors.This study has two phases: dose escalation phase and dose expansion phase.
Project description:Immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyte–associated antigen-4 and anti-programmed cell death-1 monoclonal antibodies (mAbs) agents or these combinations has improved outcomes of various cancers.However, still not a few patients fail to achieve clinical benefit, this highlights the importance of additional treatment to overcome its resistance. Previously, we showed that administration of the anti-CD4 mAb alone had strong anti-tumor effects that were superior to those elicited by CD25+ Treg depletion or other immune checkpoint mAbs in B16F10, Colon 26, or Lewis lung carcinoma subcutaneous tumor models. IT1208 (IDAC Theranostics, Tokyo, Japan) is a humanized anti-CD4 immunoglobulin G1 (IgG1) monoclonal antibody with a defucosylated Fc region, which markedly enhances antibody dependent cellular cytotoxicity. In a first-in-human, phase I, open-label, dose-escalation study, we performed transcriptomic analysis of tumors to clarify molecular responses against IT1208 monotherapy in patients with advanced solid tumors.
Project description:Immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyte–associated antigen-4 and anti-programmed cell death-1 monoclonal antibodies (mAbs) agents or these combinations has improved outcomes of various cancers.However, still not a few patients fail to achieve clinical benefit, this highlights the importance of additional treatment to overcome its resistance. Previously, we showed that administration of the anti-CD4 mAb alone had strong anti-tumor effects that were superior to those elicited by CD25+ Treg depletion or other immune checkpoint mAbs in B16F10, Colon 26, or Lewis lung carcinoma subcutaneous tumor models. IT1208 (IDAC Theranostics, Tokyo, Japan) is a humanized anti-CD4 immunoglobulin G1 (IgG1) monoclonal antibody with a defucosylated Fc region, which markedly enhances antibody dependent cellular cytotoxicity. In a first-in-human, phase I, open-label, dose-escalation study, we performed T cell repertoire analysis of T cell subsets in the tumors and peripheral blood mononuclear cells (PBMCs) to clarify T cell responses against IT1208 monotherapy in patients with advanced solid tumors.
Project description:This is a phase 1, multi-center, dose escalation, open-label study to evaluate the safety, tolerability, pharmacokinetics, and preliminary evidence of antitumor activity of JAB-3068 in adult patients with advanced solid.
Project description:This is a multi-center, open-label, dose-escalation and cohort-expansion phase I clinical study to evaluate the safety and tolerability, pharmacokinetics profile, efficacy and immunogenicity of IMM2520 in subjects with advanced solid tumors.
Project description:This study is a prospective, multi-center, open-label phase I trial designed to determine the maximun tolerated dose of IP oxaliplatin when given in combination with mFOLFIRI.