Active clinical trials for "Melanoma"

Background: The worldwide incidence of skin cancer has been rising for 50 years, in particular the incidence of malignant melanoma has increased approx. 2-7% annually and is the most common cancer amongst Danes aged 15-34. Currently there is a significant amount of misdiagnosis of skin cancer and mole cancer, and most excised skin lesions are benign. Previous studies have shown that there is no significant increase in doctors diagnostic accuracy during the first 6 years of clinical work. The resources spend on healthy people could be put to better use, if the Benign-Malignant Ratio could be lowered. This could potentially be done by better educating the doctors during their everyday clinical practice. Aim: The aim of this study is to investigate the dose/response effect of an AI augmented training and clinical feedback on the diagnostic accuracy of skin cancer and clinical decisions among doctors from specialized skin cancer centers. Research question: How much specialized doctors need to train before their diagnostic accuracy and clinical decisions change?

Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumour, metastatic disease will develop in approximately 35%-50% of the patients within 10 years. The liver is the most common site for metastases, and about 50% of the patients will have isolated liver metastases. Isolated hepatic perfusion is a regional treatment where the liver is completely isolated from the systemic circulation, allowing a high concentration of chemotherapy to be perfused through the liver with minimal systemic exposure. The introduction of modern immunotherapy in the treatment arsenal for cutaneous melanoma also creates hope for patients with uveal melanoma metastases. However, the results of immunotherapy have so far been disappointing. The reason for the low efficacy could be that uveal melanoma develops in the immune privileged eye. The hypothesis in this trial is that isolated hepatic perfusion with melphalan causes an immunogenic type of cell death by local tumour destruction while leaving the immune-system intact. This will cause an activation of the immune-system and the addition of ipilimumab and nivolumab will enhance this effect, ultimately increasing the treatment efficacy. The primary objective of this trial is to evaluate the safety and tolerability of isolated hepatic perfusion together with ipilimumab and nivolumab when given at the same time or as a sequenced regimen. The study design is a phase I randomized controlled, multicentre, open-label trial. Active follow-up will be performed for 2 years. Patients will be randomized after diagnoses of metastatic disease to one of the following treatment arms: Arm A. Patients will be treated with IHP followed by 4 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year. Arm B. Patients will be treated with 1 course of ipilimumab 3mg/kg and nivolumab 1mg/kg followed by IHP after 3 weeks and then another 3 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year.

This study evaluates whether it is safe to administer a peptide vaccine made of 6MHP and a mutated neoantigen peptide (BRAF585-614-V600E) combined with adjuvants. The adjuvants that will be used in this trial are a CD40 antibody (CDX-1140) and a toll-like receptor (TLR) 3 agonist (Poly-ICLC). The study will also investigate the effects of the vaccine and the adjuvants on the immune response. The investigators will monitor these effects by performing tests in the laboratory on participants' blood and skin tissue.

This is a phase 2, open-label, single-arm, multicenter clinical trial designed to evaluate the efficacy and safety of talimogene laherparepvec in combination with pembrolizumab following disease progression on prior anti-programmed cell death protein (anti-PD-1) therapy in unresectable/metastatic melanoma (stage IIIB-IVM1d) or prior anti-PD-1 therapy in the adjuvant setting. Subjects will be treated with talimogene laherparepvec and pembrolizumab until confirmed complete response, disappearance of all injectable lesions, documented confirmed disease progression per modified immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST), intolerance of study treatment, or 102 weeks from the first dose of talimogene laherparepvec and/or pembrolizumab, whichever occurs first.

Currently, standard treatment options available for Stage III melanoma include locoregional management (i.e. surgery) or systemic treatment (adjuvant to surgery or primarily in the case of unresectable disease). Adjuvant treatment options have shown major improvements in overall survival (OS) and relapse free survival (RFS) in resected stage III or IV melanoma. In daily practice, T-VEC monotherapy is used for unresectable Stage IIIB-IVM1a (injectable) disease, whereas Nivolumab is used for stage IV melanoma (among other systemic therapies). The next major developments are in neo-adjuvant treatment options for resectable stage III disease, where 3 small studies reported high response rates with systemic immunotherapy. This study evaluates the combination treatment of T-VEC + Nivolumab in the neo-adjuvant setting. The concept is that T-VEC can turn an immune desolate "cold" tumor into an immunogenic "hot" tumor. The hypothesis is that this will upregulate the expression of PD-L1 and make it more susceptible for treatment with an anti-PD-1 agent. The investigators believe neo-adjuvant Nivolumab + T-VEC will thus change the tumor microenvironment in patients with stage IIIB/C/D/IVM1a (AJCC 8) melanoma with resectable cutaneous or subcutaneous satellite or in-transit metastases (ITM) and/or tumor positive lymph nodes. With this trial the investigators aim to determine safety and feasibility of combination neo-adjuvant Nivolumab + T-VEC in patients with stage III melanoma with resectable ITM and/or tumor positive lymph nodes. The treatment schedule is based on 4 courses of intralesional T-VEC and 3 courses of intravenous Nivolumab. T-VEC first, in order to achieve the best synergistic effect with influx of CD8+ T cells prior to the first Nivolumab dose. T-VEC monotherapy with the dose 108 PFU/mL is given every 2 weeks (± 3) days after 3 weeks of the first T-VEC dose (with the first dose of T-VEC 106 PFU/mL to allow for seroconversion) , and Nivolumab can be given either every 2 weeks or every 4 weeks. Therefore we suggest the same dosing schedule for T-VEC and Nivolumab every 2 weeks for the purpose of this trial.

A Phase I vaccination trial in patients suffering from recently diagnosed metastatic uveal melanoma not cureable with local therapy and needing systemic therapy. IKKb-matured Dendritic Cells loaded with autologous tumor-RNA + RNA coding for defined antigens and driver mutations will be added to a standard therapy chosen by the tumor board (either checkpoint blockade or chemotherapy).

To determine the recommended Phase 2 dose (RP2D) of TBio-6517 when administered by direct injection into tumor(s) or intravenously and when combined with pembrolizumab in patients with solid tumors (RIVAL-01).

Multicentre, single-arm, open-label efficacy, pharmacokinetics, and safety study to demonstrate non-inferiority of prolgolimab 250 mg every 3 weeks versus historical data for prolgolimab 1 mg/kg every 2 weeks in patients with unresectable or metastatic melanoma, as well as collecting pharmacokinetics and safety data. The study is conducted under the same conditions as the previously conducted study BCD-100-2/MIRACULUM. This means that this Study No. BCD-100-8/FLAT has identical parameters such as: selection criteria for subjects in the study, defining the population, research centers, procedures for evaluating effectiveness and safety, permitted prior and concomitant therapy of the underlying disease.

DONIMI is a phase 1b trial testing the combination of domatinostat + nivolumab or nivolumab monotherapy in IFN-gamma signature high patients and of domatinostat + nivolumab or domatinostat + nivolumab + ipilimumab in IFN-gamma signature low patients with de-novo or recurrent macroscopic stage III cutaneous or unknown primary melanoma. The trial will include 45 stage III cutaneous or unknown primary melanoma patients with RECIST 1.1 measurable de-novo or recurrent disease (short axis lymph node metastasis ≥1.5cm). NanoString IFN-gamma signature high patients will be randomized to be treated pre-surgically for 6 weeks with nivolumab (arm A; 10 patients) or domatinostat + nivolumab (arm B; 10 patients). IFN-gamma signature low patients will be randomized to be treated pre-surgically for 6 weeks with domatinostat + nivolumab (arm C; 10 patients) or domatinostat + nivolumab + ipilimumab (arm D; 15 patients). Patients will be stratified according to center. Post-surgery (starting at week 12), the patients will start with adjuvant nivolumab or pembrolizumab for 52 weeks according to institute's standard. BRAF V600E/K mutation positive patients with no pathologic response after neoadjuvant therapy may also receive adjuvant BRAF + MEK inhibition if commercially available and according to the patient's and the treating physician's decision. Follow-up after the adjuvant therapy will be for 2 years, according to the institutes' standard. Toxicity and pathologic response rates will be descriptive. In case of 2/5 or 4/10 patients not undergoing their lymph node dissection at week 6 +/- 1 week due to treatment related toxicity, this arm will be declared unfeasible.

This study has been designed to evaluate the safety of pembrolizumab in participants in India with unresectable or metastatic melanoma and participants with non-small cell lung cancer (NSCLC) who are either untreated (programmed cell death ligand 1 [PD-L1] ≥50%) or have experienced disease progression after a platinum-containing systemic therapy (PD-L1 ≥1%).