The purpose of the study is to determine safety and tolerability of the combination of talimogene laherparepvec in combination with dabrafenib and trametinib in BRAF mutated advanced melanoma.
Name: Talimogene Laherparepvec 1 Million Pfu/Ml Inj,Susp,1Ml,Vil
Description: Up to 4mL administered on C1D1 intratumorallyType: DrugCombination
Name: Talimogene Laherparep 100 Mil Pfu/Ml 1Ml
Description: Up to 4 ML administered on Week 4 Day 1 and every 2 weeks thereafterType: DrugCombination
Name: Dabrafenib
Description: 150mg PO qdayType: DrugCombination
Name: Trametinib
Description: 2mg PO qdayType: DrugCombination
Description: Number of DLT seen in the subject population
Measure: Rate of Dose Limiting Toxicities (DLT) Time: 2 yearsDescription: per RECIST 1.1
Measure: Progression Free Survival Time: 4 yearsDescription: per RECIST 1.1
Measure: Objective Response Rate Time: 4 yearsDescription: Best change in tumor diameters
Measure: Change in tumor burden Time: 4 yearsDescription: In responding patients, time from first dose to achieving objective response
Measure: Time to Response Time: 4 yearsDescription: In responding patients, time from first evidence of objective response until progression or end of study
Measure: Duration of Response Time: 4 yearsDescription: Change in diameters of individual lesions
Measure: Lesion-level objective response Time: 4 yearsDescription: Exploratory analysis including number of participants with changes in CD8+ tumor infiltrating lymphocytes between pre-study and on-study biopsies
Measure: Biomarker analysis Time: 4 yearsSingle Group Assignment
There are 2 SNPs
Primary or recurrent Stage IIIB to IVM1c melanoma for whom surgery is not recommended 3. Activating BRAF mutation (limited to V600E or V600K mutations if being treated first-line, but can include any well-defined BRAF mutation after failure of prior immunotherapy) 4. Measurable disease defined as follows: At least one melanoma lesion that can be accurately and serially measured in one dimension and for which the longest diameter is ≥10 mm as measured by calipers, CT scan, or MRI. --- V600E ---
Primary or recurrent Stage IIIB to IVM1c melanoma for whom surgery is not recommended 3. Activating BRAF mutation (limited to V600E or V600K mutations if being treated first-line, but can include any well-defined BRAF mutation after failure of prior immunotherapy) 4. Measurable disease defined as follows: At least one melanoma lesion that can be accurately and serially measured in one dimension and for which the longest diameter is ≥10 mm as measured by calipers, CT scan, or MRI. --- V600E --- --- V600K ---