Malignant Melanoma Clinical Trials

This study will test the safety of a drug called PF-08046031 in participants with melanoma and other solid tumors that have no current approved treatment or have spread through the body. It will also study the side effects of this drug. A side effect is anything a drug does to the body besides treating the disease. The study will have 3 parts. Part A and B of the study will find out how much PF-08046031 should be given to participants. Part C will use the information from Parts A and B to see if PF-08046031 is safe and if it works to treat solid tumor cancers. Read Less

The purpose of this study is to learn about the safety and the effects of PF-08046037 alone or with sasanlimab for the treatment of certain advanced or metastatic malignancies. This study is seeking participants who: * have advanced or metastatic non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), melanoma, or pancreatic ductal adenocarcinoma (PDAC); * are able to provide tumor tissue samples; * have measurable disease. All participants will receive while at the clinic PF-08046037 alone as an intravenous (IV) infusion (given directly into a vein) or with sasanlimab as a subcutaneous (SQ) injection (given under the skin) once every 3 weeks. Participants will continue to take the study drug(s) until their cancer is no longer responding or if the patient cannot safely take them. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic. Read Less

Researchers want to learn if V940 with pembrolizumab can stop advanced melanoma from growing or spreading. Melanoma is a type of skin cancer. Advanced means the cancer has spread to other parts of the body and cannot be removed with surgery. A standard (or usual) treatment for advanced melanoma is immunotherapy. Immunotherapy is a treatment that helps the immune system fight cancer. V940 is a study treatment designed to help a person's immune system attack their specific cancer. Pembrolizumab is an immunotherapy. The goal of this study is to learn if people who receive V940 with pembrolizumab live longer without the cancer growing or spreading than people who receive placebo with pembrolizumab. A placebo looks like the study treatment but has no study treatment in it. Using a placebo helps researchers better understand the effects of a study treatment. Read Less

This is a first-in-human, phase 1a/1b, multicenter, open-label, dose escalation study of STK-012 as monotherapy and in combination therapy in patients with selected advanced solid tumors. Read Less

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. The administration of polyclonal, metabolically-fit RAPA-201 cells is a novel adoptive T cell therapy approach that is suitable for regenerative medicine efforts. RAPA-201 is a novel immunotherapy product consisting of reprogrammed autologous CD4+ and CD8+ T cells of Th1/Tc1 cytokine phenotype. 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. 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. Rapamycin-Resistance: acquisition of rapamycin-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 non-randomized, open label, multi-site, phase I/II trial of outpatient RAPA-201 immune T 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 focuses upon 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. Protocol therapy consists of six cycles of standard-of-care chemotherapy (carboplatin + paclitaxel (CP) regimen) administered in the outpatient setting 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. In the original protocol design, 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 consisted of n=10 patients; to advance to the second protocol accrual stage (accrual of an additional n=12 patients), RAPA-201 therapy must result in a tumor response (≥ PR) in at least 2 out of the 10 initial patients. As described below in the detailed description, this original protocol implementation demonstrated that RAPA-201 represented an active treatment regimen for solid tumor patients, and as such, the protocol was expanded to evaluate the combination of RAPA-201 therapy followed by anti-PD1 maintenance therapy. Read Less

This is a Phase 1, FIH, Dose Escalation and Dose Expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) effects, and preliminary antitumor activity of IK-595, a MEK/RAF molecular glue, administered orally as monotherapy in patients with advanced solid tumors with gene alterations in the RAS- MAPK pathway for whom there are no further treatment options known to confer clinical benefit. Read Less

This is a Phase 1, open-label, first-in-human study of CTX-8371 administered as a monotherapy in patients with metastatic or locally advanced malignancies. The study will be conducted in 2 cohorts: Dose Escalation and Dose Expansion. Read Less

This is a Phase 1, first-in-human (FIH), multi-center, open-label, non-randomized, dose escalation study, designed to determine the Maximum tolerated dose(MTD)/Recommended Phase 2 dose(RP2D) of LB-LR1109 and to evaluate safety, tolerability, preliminary efficacy, pharmacokinetics, immunogenicity, pharmacodynamics of LB-LR1109, and its impact on quality of life in participants with unresectable and metastatic nonsmall cell lung cancer(NSCLC), head and neck squamous cell carcinoma(HNSCC), renal cell carcinoma(RCC), urothelial carcinoma, or malignant melanoma and no available standard of care treatment options. Read Less

Patients with Small Cell Lung Cancer, High Risk Neuroblastoma, Sarcoma and Malignant Melanoma will be treated with GD2-SADA:177Lu-DOTA complex(The IMP is a two-step radioimmunotherapy, delivered as two separate products GD2-SADA and 177Lu-DOTA) to assess safety and tolerability Read Less

This clinical study is an open-label, Phase 1, dose-escalation study to determine the safety, tolerability, and efficacy of the drug product produced by Administering CRX100 alone and in combination with Pembrolizumab in advanced solid malignancies. Patients will be screened and evaluated to determine whether or not they meet stated inclusion criteria. Enrolled subjects will undergo leukapheresis to enable the ex vivo generation of CRX100. Patients with non-small cell lung cancer (NSCLC), ovarian cancer, colorectal cancer, hepatocellular carcinoma (HCC), malignant melanoma (excluding uveal melanoma), gastric cancer, triple negative breast cancer, and osteosarcoma. The study will start with monotherapy dose escalation followed by combination cohorts. Read Less

The microbiome has the potential to serve as a robust biomarker of clinical response to immunotherapy. Additionally, microbial manipulation, through diet, exercise, prebiotics, probiotics, or microbially-derived metabolites, may prove to be beneficial in promoting anti-tumor immune responses. However, large prospective studies in humans with longitudinal sample collection and standardized methods are needed to understand how microbiota and their byproducts affect cancer therapies, particularly among patients undergoing identical therapy but experiencing different outcomes. The proposed observational study builds upon these hypotheses by proposing a large cohort design to further assess the associations between the gut microbiota (composition and function), host immune system, and ICI treatment efficacy across multiple cancer types. Read Less