View clinical trials related to Malignant Melanoma.
Filter by:Melanoma is the most aggressive skin cancer. Major advances in metastatic melanoma treatment emerge from new immunotherapies that target specific immune inhibitory checkpoint receptors, mainly PD1 and CTLA-4, and overcome the exhaustion state of T cells. In this context, checkpoint inhibitors, such as Ipilimumab (anti-CTLA-4 monoclonal antibodies, mAb) and Nivolumab or Pembrolizumab (anti-PD1 mAb), have demonstrated survival benefit in advanced melanoma patients. Anti-PD1 agents and combination of anti-PD1 and anti CTLA-4 have now been approved as first line therapy in melanoma. However, the predictive factors of response to these immunotherapies remain so far elusive. Recent studies provided consistent evidence that the immune infiltration could be tested as a biomarker for such immunotherapies. Moreover, the very recent concept of tumor neoantigens as biomarkers of response to anti-CTLA-4 mAb, and potentially also to anti-PD1 or combination therapies, is promising but needs to be further explored. In this context, the aim of our program is to identify and validate an immune signature predictive of anti-PD-1 benefit in the treatment of advanced melanoma patients. To this aim, tumor samples from 120 melanoma patients enrolled prospectively, treated with anti-PD1 mAb alone or combined with anti CTLA4, will be collected as well as the corresponding peripheral blood mononuclear cells (PBMC). Tumor infiltration with immune cells will be characterized on paraffin embedded melanoma samples. The investigators will also perform whole-exome sequencing on tumors and matched PBMC samples. Our primary objective is to develop a combined immuno-signature based on an immuno-score (CD3, CD8, CD45RO…) to quantify the in situ immune populations with a dedicated image analysis system combined with the simultaneous detection of CD8-PD-1 and PD-L1 by immunofluorescence in baseline tumor samples. This will permit to predict 1-year survival of patients with advanced melanoma treated with anti-PD1 and transfer in patient's care. Our secondary objectives are: 1/ To assess the interest of the detection of tissue-resident memory (TRM) T cells (CD8-CD103) as a predictive biomarker of response and survival at 1-year; 2/ To extend the panel of neoantigens published by Snyder et al to other neoantigens using a next-generation sequencing (NGS) approach on tumor samples obtained before therapy; 3/ To establish the prognostic value of this panel of neoantigens to predict tumor response to anti-PD1 and 1-year survival; 4/ To functionally validate the identified tumor neoantigens by stimulating patient PBMC with neoantigen peptides and measuring tumor-specific T-cell reactivity; 5/ To define the best marker and/or the best combination of markers predicting the overall response rate and the survival at 12 and 18 months; 6/ To attempt to establish a correlation between immuno-signature and neoepitopes and 7/ To transfer this immune signature in routine basis if validated. Thus, our project will integrate two complementary strategies to define a robust and reliable score system for predicting anti-PD1 targeting immunotherapy response. This study will provide a unique opportunity to validate various putative biomarkers in an integrated way that could help in determining the respective value of each isolated parameter and potentially lead to the definition of a composite biomarker. The identified immune signature would be of major interest in the field of cancer immunotherapy in order to select and manage patient treatment, and to consider the benefice or toxicities expected. It will also help to identify new target antigens of effective antitumoral immune responses and to understand the resistance mechanisms established by the tumor and its influence on the response to current immunotherapies.
Phase III, open-label, randomized, controlled multi-center study of the efficacy of L19IL2/L19TNF neoadjuvant intratumoral treatment in Stage III B/C melanoma patients.
Determine the safety, tolerability, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of ACY-241 in combination with ipilimumab and nivolumab in patients with unresectable Stage III/Stage IV melanoma.
This study will investigate the influence of maintenance therapy on progression-free survival (PFS) and overall survival (OS) after combination therapy with BRAF/MEK (MAP-ERK kinase) inhibitors and PD-1 antibody pembrolizumab. In the safety phase I part the optimal dose of pembrolizumab in combination with BRAF inhibitor and MEK inhibitor and the safety of this three-drugs-combination regime will be determined. In the randomized part 2 different maintenance therapies will be tested for toxicity and efficacy. Patients with disease control after 6 months of triple therapy will be randomized to receive 2 different maintenance therapies further on, either continuation of triple therapy or administration of pembrolizumab alone.
Most patients with locally advanced or metastatic tumors succumb to their disease. Thus, there is a substantial need for novel therapeutic strategies to improve the outcome for patients with advanced or metastatic melanoma. Targeting the the Ras/Raf signalling pathway by BRAF and MEK inhibition as well as targeting immunologic checkpoint control with an antiPD-L1 antibody have emerged as treatment option. In this study the best timing for sequential use of both treatment options (BRAF/MEK inhibition and antiPD-L1 antibody) in patients with unresectable or metastatic BRAFV600 mutant melanoma will be assessed.
The purpose of this study is to evaluate if the treatment with NEO-PV-01 + adjuvant in combination with nivolumab is safe and useful for patients with certain types of cancer. The study also will investigate if NEO-PV-01 + adjuvant with nivolumab may represent a substantial improvement over other available therapies such as nivolumab alone. All eligible patients will receive NEO-PV-01 + adjuvant and nivolumab while on this trial.
IMCgp100-401 is a rollover study that is designed to provide continued access to IMCgp100 for eligible participants with advanced melanoma who have previously participated in an IMCgp100 study (parent study).
This open label extension study will give an opportunity to the participants that have responded to the treatment with Pegylated-Interferon Alfa-2a (PEG-INF) or Roferon-A in prior clinical studies NO15753 (NCT00003542) for Renal Cell Carcinoma, NO15764 (NCT number not available) and NO16006 (NCT02736721) for Chronic Myelogenous Leukemia, and NO16007 (NCT number not available) for Malignant Melanoma.
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 purpose of this study is to establish a prospective observational cohort of cancer immunotherapy patients with GI side effects in order to identify biomarkers that predict GI complications due to treatment.