“Combinations of targeted therapies continue to advance toward full regulatory approval for patients with metastatic or unresected melanoma, given the substantial benefits seen with these agents. At this time, the FDA is considering two applications for separate combinations of BRAF and MEK inhibiting agents for patients with unresectable or metastatic BRAFV600 mutation-positive melanoma.
“ ‘The future of the treatment of melanoma is clearly going to be in combinations, both for targeted therapy and for immunotherapy,’ said Jeffrey S. Weber, MD, PhD, who recently joined the NYU Langone Medical Center. ‘Already, there is an FDA-approved combination therapy that is targeted; that is dabrafenib and trametinib. There are new combinations coming up, mainly concerning CDK 4/6 and MEK inhibitors in NRAS-mutated but BRAF wild-type melanoma, which is an unmet medical need.’ “
“Talimogene laherparepvec combined with ipilimumab demonstrated tolerability at the planned doses without dose-limiting toxicities in patients with unresected, stage IIIB to IV melanoma, according to study results presented at the HemOnc Today Melanoma and Cutaneous Malignancies meeting in New York.
“The combination also demonstrated higher overall and complete response rates than typical for either agent alone, results showed.
“Talimogene laherparepvec (T-VEC, Amgen) — a systemically active oncolytic immunotherapy derived from herpes simplex virus type 1 — yielded a higher durable response (≥ 6 months) than granulocyte-macrophage colony-stimulating factor (GM-CSF) in a phase 3 melanoma trial, according to study background.
“Igor Puzanov, MD, MSCI, FACP, of the division of hematology-oncology at Vanderbilt University Medical Center, and colleagues sought to evaluate the safety and efficacy of T-VEC in combination with ipilimumab (Yervoy, Bristol-Myers Squibb).”
“Patients with unresected stage IIIb, stage IIIc or stage IV melanoma treated with talimogene laherparepvec demonstrated a durable OS advantage compared with those who received granulocyte-macrophage colony–stimulating factor, according to study results presented at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.
“Talimogene laherparepvec (T-VEC, Amgen) is a systemically active oncolytic immunotherapy derived from herpes simplex virus type-1. Upon injection directly into tumor tissue, T-VEC selectively infects and replicates in tumor cells. The virus replication leads to tumor cell lysis and exposure of tumor-specific antigens to the immune system, resulting in a local and systemic immune activation and an immune-mediated destruction of tumor cells throughout the body.
“T-VEC also is engineered to produce GM-CSF to enhance the local and systemic antitumor immune response, according to study background.”