Active clinical trials for "Melanoma"

Cutaneous melanoma is a bad prognosis skin cancer, which can be treated with immune checkpoint inhibitors (ICI), such as anti-PD-1 (nivolumab, nivo) and anti-CTLA-4 (ipilimumab, ipi). However, about 50% of patients do not respond or relapse within 3 years post therapy induction, and immune-related adverse events (irAEs), such as colitis, are triggered and can be treated with TNF inhibitor (TNFi; ie, infliximab, inflix). The pharmacodynamic impact of TNFi on the immune and clinical responses remain to be clarified. The investigators previously demonstrated that TNFi enhance the efficacy of ICI in mouse melanoma models. Based on preclinical findings, the investigators implemented two clinical trials in advanced melanoma patients, TICIMEL and MELANFalpha. In TICIMEL, patients are concomitantly treated with TNFi [certolizumab (certo) or inflix] and ICI (ipi+nivo). In MELANFalpha, patients are treated with ICI alone. Preliminary results show both tritherapies promote systemic MART-1 specific CD8 T cell responses and that certo but not inflix may improve ICI efficacy and Th1 responses. In mouse melanoma models, TNFi enhance the response to ICI. Investigators' primary objective is to decipher how certolizumab and infliximab influence ICI-dependent anti-tumor immune responses in advanced melanoma patients. The secondary objectives are to analyse the cellular and molecular impact anti-TNF have on ICI-dependent anti-melanoma immune responses and clinical activities (irAEs and efficacy). By combining mouse and human data as well ex vivo functional assays, the investigators will dissect the impact treatments have on anti-melanoma immune responses by flow cytometry and transcriptomic analyses. The investigators expect to clarify (i) the mechanisms by which TNFi enhance ICI efficacy, (ii) identify the best TNFi to be combined with ICI in advanced melanoma patients and (iii) discover TNF-dependent biomarkers of resistance.

Screen and recruitment: patients will be screened based on their prior history and intention to initiate treatment with an immune checkpoint inhibitor. Study phase: Collection of baseline demographic data, prior disease history, nature of ICI therapy, outcome data of ICI therapy (treatment disposition, toxicity, tumor response and survival). Collection of blood samples will be performed every 3 to 4 weeks for the first year on ICI therapy and every 6 to 12 weeks thereafter until the end of ICI therapy, disease progression, death or loss to follow-up. Collection of blood samples will be aligned with the visits necessary for the administration of the ICI therapy. Collection of archival melanoma metastasis tissues will be performed on a continuous basis and be triggered by availability of such tissue following therapeutic resections of melanoma metastases. Follow-up phase

The primary study objectives are to evaluate the safety and tolerability profiles of DCB-BO1301 and to determine the maximum tolerated dose (MTD) of DCB-BO1301 as add-on therapy to dacarbazine in subjects with advanced melanoma (Phase I) to evaluate the efficacy profile of DCB-BO1301 at MTD or lower dose level as add-on therapy to dacarbazine in subjects with advanced melanoma in terms of progression free survival (Phase IIa)

Prevention of melanoma can be efficient but mortality remains unchanged and 15 to 20% of patients still die from melanoma. Indeed metastatic melanoma is a heterogeneous highly and multiple mutations driven cancer. Significant survival benefit was demonstrated since 2011 with anti-CTLA4 +/- programmed death-1 (anti PD1) antibodies, B-Raf proto-oncogene, serine/threonine kinase (BRAF) and MAP-ERK kinase (MEK) inhibitors. Future improvement of advanced melanoma prognosis will rely on clinico-epidemiological studies and on biological studies to validate and identify new prognostic and predictive factors based on clinico-epidemiological and histological data, genomic host and tumor alterations, tumor microenvironment characteristics, individual immunological profile and functional imaging. In the context of marketing of costly innovative molecules, prospective collection of economic data on treatment and toxicity are required. Large biobanks collecting data from cohorts of advanced melanoma are mandatory for such projects. MELBASE is a French prospective national cohort enrolling advanced melanoma patients whose objectives are to : provide an annual instrument panel with descriptive and correlative analysis of advanced melanoma patients in France including epidemiological, clinical, biological and economic characteristics validate and identify new clinical, epidemiological, and biological prognostic factors such as genomic host and tumor alterations, tumor microenvironment characteristics, individual immunological profile in advanced melanoma evaluate the risk-benefit, quality of life, the management cost of patients treated with validated and future treatments. The project also aims to define predictive biomarkers of response and toxicity including pharmacogenetics and tumor genetics alterations, tumor microenvironment characteristics, individual immunological profile. Patients with resectable stage II or III will be enrolled since June 2023 with a 10 years follow-up. Patients with unresectable stage III or IV (resectable or not) or unresectable primary melanoma will be enrolled prospectively since March 2013 with a 10 years follow-up (up to 6000 patients) from 27 French centers.

The value of 4D body-to-whole dynamic acquisition in FDG PET / CT to differentiate progression / pseudo-progression during the first therapeutic assessment (PET1) of metastatic melanoma treated with immune checkpoint inhibitors (ICI)to predict the progression of the disease..

Biomarkers search for early diagnosis of liver metastases in patients with uveal melanoma who benefit from a follow-up tailored to their personalized risk of relapse.

Autologous monocyte-derived dendritic cells pulsed with tumor lysate (PV-001-DC) will be given to a group of 3 people. If this is found to be safe, it will be given to up to 7 other people, for a total of up to 10 people in this arm. This will be the first study of PV-001-DC. Eligible patients must be progressing after having completed prior therapy with a PD-1/PD-L1 antagonist alone or in combination with anti-CTLA-4. If the patient is positive for BRAF, the patient must have progressed on at least one BRAF inhibitor in addition to a PD-1/PD-L1 inhibitor alone or in combination with CTLA-4 for metastatic melanoma. Although other kinds of dendritic cells (DCs) have been approved to treat some forms of cancer, they have not been approved to treat melanoma. PV-001-DC is a special kind of DCs that is combined with tumor lysate. The study procedures will start with the removal of a small amount of tumor tissue processed into protein fragments (lysate). There will also be collection of white blood cells through apheresis (a procedure in which blood is drawn from a patient and separated into its different cell types), the white blood cells will be collected and the remainder returned to the patient. Dendritic cells will be grown from the collected white blood cells and combined with the lysate to form PV-001-DC. On the first day of study treatment, patients will go to the clinic and have a needle placed in a vein. The PV-001-DC product will be infused into the patient's vein. Approximately every 3 weeks, for a total of 4 treatments, patients will receive additional infusions of PV-001-DC. Patients will be at the clinic for at least 1 hour following the end of the PV-001-DC infusion and if they feel fine, they may go home. Scans will be performed during the study at different times to see if their tumors have changed in size. Patients will also have their blood and small samples of tumors tested for changes to the immune system. After 365 days, the trial will be completed for that patient. Investigators will monitor patients carefully for any harmful side effects. The side effects in people cannot be completely known ahead of time

This is a multicenter, non-interventional, retrospective study (with two prospective cohorts), including previously treated patients with melanoma, squamous cell lung cancer in the late stages (inoperable or metastatic) and Hodgkin disease at any stages. The duration of the follow-up will be 12-60 months. Data from medical records will be retrospectively collected at different points in time. The first data extraction will consist of collecting data from the initial level (before treatment with immune checkpoints inhibitors (anti-PD1 / PDl1) before the end of the recruitment period for this study (up to 3 years of follow-up). Two additional annual data collections are planned for display additional follow-up and data for patients who will survive.

This is a phase II open-label, single-arm, multi-center study of tebentafusp in HLA- A*0201 positive previously untreated (1L) untreated metastatic uveal melanoma (mUM) with an integrated circulating tumor DNA (ctDNA) biomarker.

The goal of this clinical trial is to learn about IMM60 with or without pembrolizumab in participants with advanced melanoma or non-small cell lung cancer. There are two phases: Phase 1: This phase is designed to learn about the safety of IMM60 with or without pembrolizumab and to find a safe dose to test in Phase 2. Phase 2: This phase is designed to learn whether IMM60 + pembrolizumab improves progression-free survival at 12 months compared to pembrolizumab alone in participants with non-small cell lung cancer.