A Phase 1b trial of talimogene laherparepvec in combination with dabrafenib and trametinib in advanced melanoma with an activating BRAF mutation

• Age >18 years at the time of informed consent
• Histologically confirmed diagnosis of melanoma
• Primary or recurrent Stage IIIB to IV M1c disease for whom surgery is not recommended
• Must have an activating BRAF mutation (limited to V600E or V600K mutations if subject is being treated first line, but can include any well-defined BRAF mutation after failure of prior immunotherapy)
• Measurable disease per RECIST 1.1
• Injectable disease defined as either of the following:
  • At least one injectable cutaneous, subcutaneous, or nodal melanoma lesion >10mm in longest diameter
  • Multiple injectable melanoma lesions that in aggregate have a longest diameter of >10mm
• ECOG Performance Status 0-1
• Any number of prior treatment regimens, provided that subject has not previously received T-VEC or combination of dabrafenib/trametinib
• No clinically active CNS mets
• No active herpes infection or prior complications of herpetic infections
• No known HIV, HBV, HCV
• No known severe autoimmune disease

Primary: Rate of DLTs; Secondary: PFS, ORR, TTR, DoR, lesion level responses