View clinical trials related to Advanced Solid Tumors.
Filter by:Background: - Due to its critical role in protein homeostasis pathways, p97 is a promising target for the treatment of malignancies; tumor cells are considered to be dependent on components of the protein degradation machinery to maintain homeostasis and survive. - The p97 inhibitor CB-5339 has been well characterized in in vitro and in vivo studies and had demonstrated induction of an unfolded protein response, decreased cell viability, and apoptosis. Primary Objective: -To establish the safety, tolerability, and recommended phase 2 dose (RP2D) of CB-5339 administered orally on a schedule of once daily, 4 days on and 3 days off, in patients with advanced solid tumors and lymphomas Secondary Objectives: - To evaluate the pharmacokinetic profiles of CB-5339 - To assess the preliminary antitumor activity of CB-5339 in patients with advanced solid tumors and lymphomas - To determine the effects of CB-5339 on the ubiquitin proteasome system and markers of cell death in pre- and post-treatment tumor biopsies and peripheral blood mononuclear cells (PBMCs) Exploratory Objectives: -To evaluate potential associations between CB-5339 activity and genomic alterations assessed in circulating tumor DNA Eligibility: Patients >= 18 years of age must have histologically documented solid tumors whose disease has progressed on standard therapy or for which there is no available standard therapy or therapy known to prolong survival; or aggressive lymphoma who have refused or have no remaining curative options. Patients with indolent lymphomas must have undergone 3 or more prior regimens of therapy Study Design: - CB-5339 will be administered orally on a schedule of once daily, 4 days on and 3 days off, in 28-day cycles. - The trial will follow an accelerated titration design, changing to a traditional 3+3 dose escalation design (3-6 patients per cohort) once specified toxicity criteria are met. A separate 15-patient expansion cohort will further explore pharmacodynamic endpoints and obtain additional pharmacokinetic data at the RP2D. - Once pharmacodynamic data are available at the RP2D, additional expansion cohorts may be considered to explore pharmacodynamic endpoints at lower dose levels (a protocol amendment will be submitted for these changes to the trial design). - Blood samples will be obtained for pharmacokinetic and pharmacodynamic analyses and to isolate circulating tumor DNA. Tumor biopsies will be collected at baseline and 4-6 hours after drug administration in the expansion cohort only; an optional biopsy may be collected at disease progression. - Pharmacodynamic effects of CB-5339 will be assessed through a panel of markers including accumulation of lysine-48 (K48) specific polyubiquitinated substrates in the cytosol, upregulation of transcription factor CHOP in nucleus, and appearance of cleaved caspase-3 in the cytosol.
This is an open-label, two-part study to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of SHR-A1811 and preliminary anti-tumor efficacy in HER2 expressing or mutated advanced malignant solid tumor subjects.
This is a study to evaluate the maximum tolerated dose (MTD) , occurrence of all adverse events (AE) and serious adverse events (SAE) , pharmacokinetic parameters and antitumor effect of TQB3558 tablets in Chinese adult patients with advanced solid tumors .The study is divided into phase Ia and phase Ib. Phase Ia: dose escalation period, to evaluate the safety and tolerability of TQB3558 tablets, determine MTD; Phase Ib: effectiveness exploration period, to expand the safe and effective dose group, recommend appropriate dosage and method for subsequent clinical research.
The purpose of the study is to characterize the safety and pharmacokinetic (PK) profile of UCB6114 administered as monotherapy or in combination with selected standard of care (SOC) regimens.
The purpose of this study is to evaluate the safety，tolerability, pharmacokinetics, and preliminary efficacy of KC1036 in participants with advanced recurrent or metastatic solid tumors. The trial will be divided into three parts: dose-escalation phase, dose-expansion phase, RP2D-extension phase.
To evaluate the safety and tolerability of AMG 256 in adult participants and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
To assess the Safety, Tolerability, and Pharmacokinetic-pharmacodynamic Profile and efficacy of JPI-547 in patients with advanced solid tumor.
The study was designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of CSPCHA131 alone or plus chemotherapy in patients with advanced solid tumors.
This is a 3-cohort, multicenter, Phase 1 study of the effect of tesetaxel, an investigational, orally administered taxane, on the corrected QT (QTc) interval and the potential effect of food, a cytochrome P450 (CYP) 3A inhibitor (itraconazole), and a CYP3A inducer (rifampin) on tesetaxel pharmacokinetics (PK) in adult patients with advanced solid tumors.
This is a safety, pharmacokinetic and pharmacodynamic study designed to estimate the maximum tolerated dose (MTD), and determine the Recommended Phase 2 Dose (RP2D) of SYHA1801, a BRD4 inhibitor in patients with advanced solid tumors.