View clinical trials related to Triple Negative Breast Cancer.
Filter by:This study aims to investigate if olaparib plus pembrolizumab will maintain the clinical benefit achieved after induction therapy with Albumin-bound paclitaxel combined with cisplatin(AP) regimen and pembrolizumab in previously untreated locally advanced, recurrent or metastatic TNBC population with PD-L1 CPS≥1.
The therapy of solid tumors has been revolutionized by immune therapy, in particular, approaches that activate immune T cells in a polyclonal manner through blockade of checkpoint pathways such as PD-1 by administration of monoclonal antibodies. In this study, the investigators will evaluate the adoptive transfer of RAPA-201 cells, which are checkpoint-deficient polyclonal T cells that represent an analogous yet distinct immune therapy treatment platform for solid tumors. RAPA-201 is a second-generation immunotherapy product consisting of reprogrammed autologous CD4+ and CD8+ T cells of Th1/Tc1 cytokine phenotype. First-generation RAPA-101, which was bred for resistance to the mTOR inhibitor rapamycin, demonstrated clear anti-tumor effects in multiple myeloma patients without any product-related adverse events. Second-generation RAPA-201, which have acquired resistance to the mTOR inhibitor temsirolimus, are manufactured ex vivo from peripheral blood mononuclear cells collected from solid tumor patients using a steady-state apheresis. RAPA-201 is also being evaluated for the therapy of relapsed, refractory multiple myeloma and was granted Fast Track Status by the FDA for this indication. The novel RAPA-201 manufacturing platform, which incorporates both an mTOR inhibitor (temsirolimus) and an anti-cancer Th1/Tc1 polarizing agent (IFN-alpha) generates polyclonal T cells with five key characteristics: 1. Th1/Tc1: polarization to anti-cancer Th1 and Tc1 subsets, with commensurate down-regulation of immune suppressive Th2 and regulatory T (TREG) subsets; 2. T Central Memory: expression of a T central memory (TCM) phenotype, which promotes T cell engraftment and persistence for prolonged anti-tumor effects; 3. Temsirolimus-Resistance: acquisition of temsirolimus-resistance, which translates into a multi-faceted anti-apoptotic phenotype that improves T cell fitness in the stringent conditions of the tumor microenvironment; 4. T Cell Quiescence: reduced T cell activation, as evidence by reduced expression of the IL-2 receptor CD25, which reduces T cell-mediated cytokine toxicities such as cytokine-release syndrome (CRS) that limit other forms of T cell therapy; and 5. Reduced Checkpoints: multiple checkpoint inhibitory receptors are markedly reduced on RAPA-201 cells (including but not limited to PD-1, CTLA4, TIM-3, LAG3, and LAIR1), which increases T cell immunity in the checkpoint-replete, immune suppressive tumor microenvironment. This is a Simon 2-stage, non-randomized, open label, multi-site, phase I/II trial of RAPA-201 T immune cell therapy in patients with advanced metastatic, recurrent, and unresectable solid tumors that have recurred or relapsed after prior immune therapy. Patients must have tumor relapse after at least one prior line of therapy and must have refractory status to the most recent regimen, which must include an anti-PD-(L)1 monoclonal antibody. Furthermore, accrual is limited to solid tumor disease types potentially amenable to standard-of-care salvage chemotherapy consisting of the carboplatin + paclitaxel (CP) regimen that will be utilized for host conditioning prior to RAPA-201 therapy. Importantly, carboplatin and paclitaxel are "immunogenic" chemotherapy agents whereby the resultant cancer cell death mechanism is favorable for generation of anti-tumor immune T cell responses. Thus, the CP regimen that this protocol incorporates is intended to directly control tumor progression and indirectly promote anti-tumor T cell immunity. The CP regimen is considered standard-of-care therapy for the following tumor types, which will be focused upon on this RAPA-201 protocol: small cell and non-small cell lung cancer; breast cancer (triple-negative sub-type or relapse after ovarian ablation/suppression); gastric cancer (esophageal and esophageal-gastric-junction adenocarcinoma; gastric adenocarcinoma; esophageal squamous cell carcinoma); head and neck cancer (squamous cell carcinoma of oral cavity, larynx, nasopharynx, and other sites); carcinoma of unknown primary; bladder cancer; and malignant melanoma. Protocol therapy consists of six cycles of standard-of-care chemotherapy (carboplatin + paclitaxel (CP) regimen) administered every 28 days (chemotherapy administered on cycles day 1, 8, and 15). RAPA-201 cells will be administered at a target flat dose of 400 X 10^6 cells per infusion on day 3 of cycles 2 through 6. A sample size of up to 22 patients was selected to determine whether RAPA-201 therapy, when used in combination with the CP regimen, represents an active regimen in solid tumors that are resistant to anti-PD(L)-1 checkpoint inhibitor therapy, as defined by a response rate (≥ PR) consistent with a rate of 35%. The first stage of protocol accrual will consist of n=10 patients; to advance to the second protocol accrual stage, RAPA-201 therapy must result in a tumor response (≥ PR) in at least 2 out of the 10 initial patients.
The study is a single arm, nonrandomized phase II prospective study, with the goal of investigating the role of screening brain MRIs in neurologically asymptomatic patients with metastatic breast cancer.
This study is a genetic analysis of aberrations in circulating tumor DNA (ctDNA) in patients in Asian countries. This study protocol is divided into parts describing several subanalyses that differ in terms of cancer types, analytical methods, participating countries, and participating institutions.
This is a Phase 1/2, multi-center, open-label, dose-escalation and expansion study to evaluate safety and tolerability, PK, pharmacodynamic, and early signal of anti-tumor activity of MDNA11 alone or in combination with a checkpoint inhibitor in patients with advanced solid tumors.
This is a phase 1/2, open-label, multi-center, first-in-human, two-stage (Part 1: dose escalation and Part 2: dose expansion) study evaluating multiple doses and schedules of intravenously (IV) administered HMBD-002, with or without pembrolizumab, in patients with advanced solid tumors (i.e., locally advanced and unresectable, or metastatic).
This is a multi-centre Phase I dose finding and proof-of-concept study of the combination of ASTX660 together with Pembrolizumab with expansion cohorts testing preliminary efficacy in immune-refractory cancers, triple negative breast cancer (TNBC), cervical cancer, and glioblastoma. In contrast to the existing studies combining first-generation cIAP1/2 selective Smac mimetics with immune check point inhibitors, the ASTEROID Phase I clinical trial will be the first trial utilising triple cIAP1/2 and XIAP blockade by ASTX660 as a strategy to maximise immunogenic cell death and the generation of an efficient adaptive immune response. ASTX660 is not simply being used to repeat the data already being acquired with other first generation Smac mimetics. In contrast, we will investigate more in depth the mechanisms by which ASTX660 elicits its therapeutic effects both on tumour and on the host immune system. This will be critical to determine the best strategy to pursue in future later stage tumour specific trials of IAP antagonists in combination with immunotherapy, and to ensure appropriate molecular stratification biomarkers for the greatest benefit to patients.
Immunotherapy (IO), such as treatment with anti-PD-1, PD-L1, or CTLA-4 inhibitors, is a rapidly expanding treatment for multiple metastatic cancers with improved survival for certain cancers. However, the optimal duration of immunotherapies is currently unknown. Our hypothesis is that a reduced dose intensity of IO could be as effective as the current standard treatment in term of prevention of the disease progression. If proved right, this study will have a positive medico-economic impact by reduction of the costs associated with the treatment and the toxicity, and an increase of the patients' quality of life.
This phase I trial is designed in two parts. First as an open-label, dose escalation trial of MEM-288 monotherapy in which investigators aim to find the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Subjects with selected solid tumors including non-small cell lung cancer (NSCLC) who have a tumor lesion which is accessible for injection will undergo intratumoral injection of MEM-288. Following completion of the monotherapy study portion of the study, an expansion arm is designed to test MEM-288 with concurrent anti-PD-1 (nivolumab) therapy for patients with first relapsed or refractory advanced/metastatic NSCLC following front-line anti-PD-1/PD-L1 with or without concurrent chemotherapy. The study rationale is that the oncolytic effect of MEM-288 combined with the presence of CD40L and type 1 interferon (IFN) in injected tumors will provide a strong signal for dendritic cell (DC)-mediated T cell activation leading to generation of systemic anti-tumor T cell responses with broad specificity akin to what is observed in the abscopal effect. Further study rationale is the anti-tumor effect of MEM-288 will be enhanced by nivolumab by reversing T cell exhaustion.
This is a Phase II, open-label, three-arm parallel study evaluating the efficacy and safety of combined treatment (sodium cromoglicate, choline, or efavirenz) with immune checkpoint inhibitor in mTNBC (triple negative breast cancer) patients who progressed during previous immune checkpoint inhibitors.