Melanoma Stage Iii

This Phase 2, multi-center, single-arm study evaluates the safety, tolerability, and activity of neoadjuvant PRTX007 in combination with pembrolizumab in participants with resectable Stage III melanoma. Neoadjuvant immunotherapy has demonstrated improved clinical outcomes compared with adjuvant-only approaches, but there remains a need to enhance pathologic response rates without significant added toxicity. Participants will receive oral PRTX007, a Toll-like receptor 7 (TLR7) agonist prodrug, administered in combination with intravenous pembrolizumab prior to surgical resection. The primary objective is to determine the major pathologic response (MPR) rate following neoadjuvant therapy. Secondary objectives include evaluation of safety, pathologic complete response, event-free survival, overall survival, pharmacokinetics, and immune-related biomarkers. This study aims to determine whether the addition of PRTX007 to pembrolizumab improves antitumor immune responses and clinical outcomes in patients with Stage III melanoma.

In this first-in human, phase I/IIa study, the safety and efficacy of \[212Pb\]VMT01, an alpha-particle emitting therapeutic agent targeted to melanocortin sub-type 1 receptor (MC1R) is being evaluated as a monotherapy and in combination with nivolumab in subjects with unresectable and metastatic melanoma.

This phase II trial studies how well binimetinib and imatinib work in treating patients with stage III-IV KIT-mutant melanoma that cannot be removed by surgery (unresectable). Binimetinib and imatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving binimetinib and imatinib may help treat patients with KIT-mutant melanoma.

The purpose of this study is to determine if neoadjuvant (treatment before surgery) immunotherapy treatment based on tumor biomarkers results in better participant outcomes. Immunotherapy is the treatment of disease by using a person's own immune system. This study is divided into 2 sub-studies/parts designated Part 1 and Part 2 that will enroll in sequence starting with Part 1 followed by Part 2.

The purpose of this study is to find out if the administration of Interleukin-2 concurrently with ipilimumab followed by Nivolumab will result in improved anti-cancer activity and if it is effective for advanced melanoma.

This is a phase 2, single-arm, open label clinical trial determining efficacy of Cyclophosphamide and Pembrolizumab in subjects with melanoma.

The purpose of this study is to assess rate of disease relapse and hazard rate of disease relapse after neoadjuvant therapy based on the statuses of pathologic complete response or non-pathologic complete response, and postoperative adjuvant therapy.

The purpose of this research study is to determine if analysis of PET/CT scans and testing of blood samples in people with melanoma that has spread in their body can help researchers determine which patients are more or less likely to respond to immunotherapy and are more or less likely to have side effects. 24 participants will be enrolled and be on study until approximately 4 weeks after their first dose of Immune Checkpoint Inhibitor therapy.

The goal of this Long-Term Follow-Up Trial is to assess long-term safety and efficacy of Miltenyi CAR T treatment.

The purpose of this study is to determine how beta-glucan affects the immune system in subjects with melanoma.

The primary objective of this Phase 1 clinical trial is to evaluate the feasibility and tolerability of a novel generation of gene-modified tumor infiltrating lymphocytes (TILs) in a cohort of 10 patients aged 18-75 diagnosed with unresectable or metastatic melanoma. TILs will undergo transduction with the Interleukin-7 (IL-7) gene, for IL-7 production upon antigen engagement. Participants will undergo: * screening * tumor operation following autologous TIL production (incl. transduction) - takes approximately 4-6 weeks * admission for lymphodepleting chemotherapy (Cyclophosphamide and Fludarabine phosphate), TIL infusion and high-dose IL-2 infusions for a maximum of 6 doses * Following treatment, patients will undergo systematic and regularly planned assessments, encompassing clinical evaluation, biochemistry analyses, and PET/CT scans. This thorough follow-up regimen will be continued until any of the following events occur: progressive disease, withdrawal from study, or end of study, which spans a duration of 15 years for trials involving genetically modified organisms.

KB707-01 is a Phase 1/2, open-label, multicenter, dose escalation and expansion study. The study will evaluate the safety and tolerability of KB707 in adults with locally advanced or metastatic solid tumors who have progressed on standard of care therapy, cannot tolerate standard of care therapy, refused standard of care therapy, or for whom there is no standard of care therapy as well as the safety, tolerability, preliminary efficacy, and immunologic effect of KB707 administered in combination with Opdualag to subjects with unresectable or metastatic melanoma. Subjects in dose escalation (Cohorts 1 through 3) and dose expansion (Cohort 4) will receive intratumoral injections of KB707 approximately every three weeks. Cohorts 1 through 4 are closed to new enrollment. Dose expansion Cohort 5 and Cohort 6 will evaluate subjects with advanced melanoma. Subjects in Cohort 5 will receive intratumoral injections of KB707 biweekly (q2w), delivered in combination with Opdualag (dosed every q4w per prescribing information). Subjects in Cohort 6 will receive intratumoral injections of KB707 biweekly (q2w), delivered in combination with Keytruda (dosed every q6w per prescribing information). All subjects will be treated until disease progression, death, unacceptable toxicity, symptomatic deterioration, achievement of maximal response, subject choice, Investigator decision to discontinue treatment, or the Sponsor determines to terminate the study.

This is an observational, multicentre epidemiological study with a longitudinal cohort in which information will be retrieved from medical records of patients with advanced metastatic or unresectable melanoma at first diagnosis.

In this study the aim is to investigate whether transfer of the microbiota of either responder or non-responder patients via fecal microbiotica transplantation (FMT) can convert the response to immunotherapy in immune checkpoint inhibitors (ICI) refractory metastatic melanoma patients. This is a randomized double-blind intervention phase Ib/IIa trial in ICI refractory metastatic melanoma patients receiving either FMT of an ICI responding or FMT from an ICI non-responding donor, in combination with ICI. Following randomization, patients will receive vancomycin 250 mg, four times daily for 4 days (day -5 up until day -2), and undergo bowel clearance on day -1 (in total 1L MoviPrep). The FMT, either derived from donor group R (who showed a good response on anti-PD-1 therapy) or donor group NR (who showed progression on anti-PD-1 therapy), will be performed by a gastroenterologist using esophagogastroduodenoscopy. A total amount of 198mL (containing a total of 60 gram feces) will be used for transplantation. Anti-PD-1 treatment will be continued according to the patient's regular treatment schedule. Evaluation of safety and response to treatment will be performed.

Safe Stop IPI-NIVO Trial: Early discontinuation of nivolumab upon achieving a (confirmed) complete or partial response in patients with irresectable stage III or metastatic melanoma treated with first-line ipilimumab-nivolumab

Rheumatologic adverse events are expected to affect between 3% and 7.5% of patients undergoing immunotherapy and are likely to be underdiagnosed. The main aim of this observational prospective study is to investigate the clinical and ultrasonographic incidence of rheumathologic immune related adverse events in a cohort of patients affected by stage IIB, IIC, III and IV melanoma undergoing treatment with immune-checkpoint inhibitors. Patients will: * receive immune-checkpoint inhibitor therapy, according to disease stage and current National Guidelines. * undergo dermatologic visit prior to the start of immune-checkpoint inhibitor therapy and at scheduled follow-ups. * undergo rheumatologic visit prior to the start of immune-checkpoint inhibitor therapy and at scheduled follow-ups. * receive a quality of life questionnaire (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 version 3.0) prior to the start of immune-checkpoint inhibitor therapy and at scheduled follow-ups.

The trial will test a paradigm-changing in vitro diagnostic device for Liquid Biopsy enabling facile simultaneous detection of protein and nucleic acid analytes with sensitivity at single-molecule level, e.g. not achievable with any alternative technology. A novel affinity-mediated transport amplification (AMT) method will be tested allowing for the multiplexed quantification of rare biomarkers circulating in blood. The Versilib AMT photonic biosensor will test two analytes: the known actionable DNA mutation BRAF p.V600E, and a melanoma-restricted protein antigen. The results will be compared to digital PCR and ELISA methods.

The trial aims to evaluate the efficacy of single agent L19IL2, single agent L19TNF, and combination L19IL2+L19TNF given concurrently with anti-PD1 therapy compared to historical control of anti-PD-1 re-challenge alone for anti-PD1 refractory unresectable stage III-IV melanoma.

BERING-MELANOMA - designed as a prospective, longitudinal, non-interventional study - investigates real-world effectiveness, quality of life, safety and tolerability of encorafenib plus binimetinib in unresectable advanced or metastatic BRAF(Rapidly Accelerated Fibrosarcoma isoform B)-V600-mutant malignant melanoma after commercial availability of these two products in Germany, Austria and Switzerland. The study focusses on the documentation of the first and second line setting (i.e. after one line of prior checkpoint inhibition) by documenting patients treated according to the SmPC (Summary of Product Characteristics).