Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Trametinib

Dabrafenib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Pembrolizumab combined with a short scheme of dabrafenib+trametinib

Pembrolizumab combined with an intermediate scheme of dabrafenib+trametinib

Pembrolizumab combined with a long scheme of dabrafenib+trametinib

Biopsies will be taken during screening, before randomization, at week 8 (only arm 2-4) after 12 weeks, at week 18 and if PD.

Biopsy

Blood will be taken for PBMCs during screening (twice), before randomization, at weeks 12 at week 18 and if PD.

Blood taking

Christian U. Blank, Prof.

This is a Phase 2 trial consisting of 24 patients receiving the combination of dabrafenib + trametinib + pembrolizumab in 3 different dosing schemes and 8 patients receiving pembrolizumab standard monotherapy. All patients start with pembrolizumab standard therapy for 6 weeks and will then be randomized to continue pembrolizumab monotherapy or to receive additional intermitted/short-term dabrafenib + trametinib.

Stratification will be baseline LDH level and baseline PD-L1 expression.

Study Comparing Pembrolizumab With Dual MAPK Pathway Inhibition Plus Pembrolizumab in Melanoma Patients

Phase 2 Study Comparing Pembrolizumab With Intermittent/Short-term Dual MAPK Pathway Inhibition Plus Pembrolizumab in Patients Harboring the BRAFV600 Mutation

As the short addition of dabrafenib+trametinib will induce for short time tumor regressions we will analyze cohorts 2-4 with a second baseline, namely the end of the targeted therapy at week 12, for progression free survival using to RECIST 1.1

In addition to the primary readout (broadening of the melanoma-specific T cell response in peripheral blood), we will analyze the effect of the different therapy schemes on tumor immune cell infiltration (IHC for CD3, CD4, CD8, CD68, FoxP3, PD-L1, PD-L2, PD-1, CD11b, HLA).

Safety as measured by SUSARs during treatment week 0 till week 18.

Feasibility as measured by adherence to the timelines in the study protocol (week 0 till week 18).

Readout will be the alterations in magnitude or breadth of the self-antigen specific T cell responses in the time interval pre-treatment to week 18 intrapatient, and interpatient, pembrolizumab only (cohort 1) versus pembrolizumab plus intermittent dabrafenib/ trametinib (cohorts 2-4). To this purpose, we will analyze melanoma antigen-specific T cells responses by HLA-A2-restricted MHC-tetramer staining.

Rates of response at week 6, week 12, week 18 according to RECIST 1.1 criteria

Progression-free survival (PFS) starting from randomization to progression using RECIST 1.1 criteria.

Spots Global Cancer Trial Database for blood taking

Every month we try and update this database with for blood taking cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.