Neoadjuvant T-VEC in High Risk Early Melanoma

Recruiting in Palo Alto (17 mi)

Overseen BySepideh Gholami, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: University of California, Davis

Stay on your current meds

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?Despite the recent notable advances in the treatment of advanced melanoma with application of growing immunotherapies, patterns of response and factors resulting in treatment failure are poorly understood. Moreover, the application of these therapeutics has been limited in the neoadjuvant setting, particularly in earlier stage disease, even though this strategy has improved tolerance and efficacy with other modalities of therapy in other cancer types. Survival remains significantly poorer for thicker and ulcerated lesions with T3b and T4 lesions demonstrating less than 50% survival at 5 years independent of other prognostic indicators. Oncolytic viral therapies (OVT) stimulate or suppress the immune system in different ways to stop cancer cells from growing and intra-lesional OVT has demonstrated comparable efficacy and durability with greater tolerability than most effective systemic therapy. Talimogene laherparepvec (T-VEC) is the only phase III approved intra-lesional therapy in melanoma and has demonstrated significantly improved overall response rate (64%) and bystander effect (34% in uninjected lesions) in the therapeutic setting for advanced disease. The investigators propose an open-label, Phase 2 study of talimogene laherparepvec (T-VEC), in the neoadjuvant setting for patients with high-risk, resectable primary and cutaneous melanoma prior to definitive excision. The central hypothesis of this proposal is that neoadjuvant intra-lesional therapy with T-VEC in high risk early stage melanoma will effectively treat local and subclinical distant disease by enhanced immune recognition, immunomodulation of the nodal basin, and still allow for standard of care surgery. The primary aim of this study will be to evaluate for histologic response of melanoma with secondary aim to determine changes in immune response and draining sentinel nodes as well as relationship of immune phenotype to response rate, stage and nodal burden. The investigators plan for thorough exploratory analysis of genetic and microenvironmental changes to identify actionable targets in incomplete as well as evaluation of changes in sentinel burden and subsequent rates of locoregional disease control, recurrence-free survival and overall survival in long term follow up. The investigators predict that histologic clearance of the primary tumor in the surgical specimen will be associated with improved RFS.