Active clinical trials for "Mesothelioma"

The proposed study will evaluate the safety and feasibility of neoadjuvant nivolumab +/- ipilimumab in resectable MPM. In addition, maintenance nivolumab will be administered for 1 year following completion of standard bi-/tri-modality therapy.

Rationale: Pemetrexed is a multi-targeted folate antagonist, which is primarily indicated for the treatment of advanced non-small cell lung cancer (NSCLC) and mesothelioma. Dosing of cytotoxic agents like pemetrexed requires balancing the dual risk of sub-therapy and toxicity. Administration of pemetrexed to patients with a creatinine clearance <45 ml/min is currently not advised. Pemetrexed is dosed based on body surface area (BSA), while renal function and dose are the sole determinants for systemic exposure. This causes 3 major issues: In patients with renal dysfunction, BSA-based dosing may lead to haematological toxicity Patients have to discontinue treatment due to declining renal function, and are withheld effective treatment Even in patients with adequate renal function (GFR >45 ml/min) treatment may be improved by individualized dosing based on renal function, resulting in less toxicity. Also, BSA-based dosing may lead to ineffective therapy in patients with above average renal function. The investigators aim to address these problems. Objective: The overall main objective is to develop a safe and effective individualized dosing regimen for pemetrexed. Study design:IMPROVE-I is a single arm phase II pharmacokinetic safety study using a Simon two stage design to assess the feasibility of renal function-based dosing of pemetrexed in renal impaired patients. Study population: IMPROVE-I includes 23 patients with NSCLC or mesothelioma with an estimated creatinine clearance <45ml/min that meet all other requirements for pemetrexed treatment. Intervention:Patients will be treated with pemetrexed, with dosing based on renal function. As a safety measure, the first dose will be calculated to 50% exposure. After administration, safety and pharmacokinetics are assessed. If tolerated well, dose escalation to reach 100% exposure is performed, including assessment of safety and pharmacokinetics. Main study endpoints: The fraction (percentage) of patients with attainment of therapeutic exposure. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The investigators consider the extra burden from participating in the planned studies limited. The extra interventions compared to routine care, consist of sampling extra blood. The pharmacokinetic assessments require placement of one additional intravenous catheter. To ensure minimal impact of study participation on daily life, a limited sampling strategy will be used. Patients may benefit from participating in IMPROVE I and -II, as they will be treated with a potentially safe and effective drug that is dosed individually, which prevents toxic exposure

Phase I study to establish safety and feasibility of both intravenous administration and local delivery of lentiviral transduced huCART-meso cells with or without lymphodepletion.

This study will test the safety, including side effects, and determine the characteristics of a drug called PRO1184 in participants with solid tumors. Participants will have solid tumor cancer that has spread through the body (metastatic) or cannot be removed with surgery (unresectable). This study will have two parts. Part A of the study will find out how much and how frequently PRO1184 should be given to participants. Part B will use the dose and schedule found in Part A to find out how safe PRO1184 is and if it works to treat solid tumor cancers.

TC-510 is a novel cell therapy that consists of autologous genetically engineered T cells expressing two synthetic constructs: first, a single-domain antibody that recognizes human Mesothelin, fused to the CD3-epsilon subunit which, upon expression, is incorporated into the endogenous T cell receptor (TCR) complex and second, a PD-1:CD28 switch receptor, which is expressed on the surface of the T cell, independently from the TCR. The PD-1:CD28 switch receptor comprises the PD-1 extracellular domain fused to the CD28 intracellular domain via a transmembrane domain. Thus, the switch is designed to produce a costimulatory signal upon engagement with PD-L1 on cancer cells.

This is a multicenter, open-label study conducted in 3 phases: Dose escalation stage: The stage contain 4 cohorts, each cohort divided into 2 groups （group A, single dose and Group B, multiple dose）.Dose escalation will use a 3+3 design to evaluate escalating doses of T3011.Cohorts of three subjects will be enrolled at each T3011 dose level with expansion to six subjects, if necessary, to assess toxicity. Total enrollment will depend on the toxicities observed, with approximately 4-24 evaluable subjects enrolled in dose escalation stage. Dose extension stage: The SMC will evaluate the available safety and preliminary efficacy data and initiate dose-expansion studies for the appropriate indications Phase IIa: To explore the safety of intravenous administration and expand the study in other indications. the stage will be carried out gradually based on the data obtained from the phase I study.

Study of NGM438 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumors

This is a first in human phase 1 study of AG01 an anti-Progranulin/Glycoprotein88 (PGRN/GP88) antibody in patients with advanced solid tumors. AG01 is a recombinant monoclonal antibody expressed in a CHO production cell line. The antibody AG01 binds to human PGRN/GP88, expressed on cancer cells. This study will have a dose escalation portion (1A) to evaluate maximum tolerated dose (MTD) and/or maximum administered dose (MAD), the safety and tolerability of AG01treatment before the dose expansion portion (1B) of the study is initiated. The dose escalation portion of this study (1A) will also be used to determine the recommended phase 2 dose (RP2D) of AG01 antibody to be evaluated in the cohort expansion portion (1B).

This is a single institution, single-arm, window of opportunity pilot trial of pembrolizumab in patients with resectable malignant pleural mesothelioma. All patients will undergo a pretreatment PET/CT scan for clinical staging and a VATS procedure to acquire pretreatment tissue. Three cycles of pembrolizumab will then be administered (200 mg IV every 21 days). A PET/CT scan will then be repeated to assess response to pembrolizumab and then surgical resection will be performed at least 4 weeks after the third dose of pembrolizumab. Standard adjuvant chemotherapy consisting of cisplatin and pemetrexed for 4 cycles (every 21 days) will be given following surgery. After the completion of standard chemotherapy, optional adjuvant treatment with pembrolizumab will be given to eligible patients for 1 year post-surgery.

This study is an open-label, multi-arm, parallel cohort, dose validation and expansion design. The study is modular in design, allowing evaluation of the safety, efficacy and pharmacokinetics (PK) of NUC-3373 in combination with other agents for the treatment of patients with different tumour types. Each module is designed to evaluate a different NUC-3373 combination and consists of a dose-validation phase (Phase Ib) and a dose-expansion phase (Phase II). Phase Ib of each module will determine the safety and tolerability of the combinations for further clinical evaluation in Phase II. Approximately 6-20 evaluable patients will be enrolled in the Phase Ib stage of each module to determine safety, tolerability, and preliminary efficacy of NUC-3373 in combination with other agents. Each module will then move into Phase II to enable a further assessment of safety and efficacy in approximately 20-40 patients. Module 1 will assess NUC-3373 + leucovorin (LV) in combination with pembrolizumab for the treatment of patients with advanced/metastatic solid tumours who have progressed on ≤2 prior therapies for metastatic disease, that may have included 1 prior immunotherapy-containing regimen (either monotherapy or in combination with chemotherapy) or who have not progressed but where addition of NUC-3373 + LV to standard pembrolizumab monotherapy may be appropriate (e.g., patients who could not tolerate post- immuno-oncology (IO) standard of care therapy). Module 2 will assess NUC-3373 + LV in combination with docetaxel for the treatment of patients with advanced/metastatic non-small cell lung cancer (NSCLC) or pleural mesothelioma who have progressed on, or were unable to tolerate, 1 or 2 prior lines of cytotoxic chemotherapy-containing regimens for advanced/metastatic disease. The opening of each module will be at the discretion of the Sponsor. Further modules may be added as non-clinical and clinical data become available to support additional NUC-3373 combinations and tumour types.