Neoadjuvant Combination Immunotherapy for Stage III Melanoma

Study Overview
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Brief Summary
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Determine safety and efficacy of pre-operative combination immunotherapy with Talimogene Laherparepvec (T-VEC)/Pembrolizumab given prior to complete lymph node dissection in resectable stage 3 cutaneous melanoma with clinically apparent lymph node metastases.

Detailed Description
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This is a single arm Phase 2 study of pre-operative combination immunotherapy with pembrolizumab and T-VEC given for 6 months prior to complete lymph node dissection for stage 3 resectable cutaneous melanoma with clinically apparent lymph node metastases.

Official Title
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Neoadjuvant Combination Immunotherapy for Stage III Melanoma

Conditions
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Cutaneous Melanoma

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: Talimogene Laherparepvec


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age, any race or sex, who have pathologically confirmed cutaneous melanoma ECOG performance status of 0 or 1 Adequate hematologic, hepatic, renal and coagulation function Must have measurable disease and have an injectable target lymph node for intralesional therapy administration Primary melanoma has been resected Pathologically confirmed resectable stage III disease, clinically apparent. Resectability is at the discretion of the treating surgeon who is a melanoma specialist. Stage III disease can be at time of diagnosis of primary melanoma or a recurrence after initial treatment of stage I-II disease. BRAF mutant or wild type allowed (mutations status not necessary for enrollment) Signed, written informed consent Exclusion Criteria: Cannot have metastatic (AJCC M1) disease No primary mucosal or uveal melanoma No evidence of melanoma associated with immunodeficiency state or history or other malignancies (other than non-melanoma skin cancer) within the past 3 years May not have been previously treated with T-VEC, any other oncolytic virus, pembrolizumab, or any other PD-1, PD-L1, or PD-L2 inhibitor Must not have a history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease, document history of autoimmune disease or syndrome requiring systemic treatment in the past two years (i.e. use of disease modifying agents, steroids, or immunosuppressive agents) except vitiligo or resolved childhood asthma/atopy, or evidence of clinically significant immunosuppression Must not have active herpetic skin lesions or prior complications of herpetic infection and must not require intermittent or chronic treatment with an anti-herpetic drug (e.g. acyclovir) other than intermittent topical use

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination T-VEC/Pembrolizumab<br>Pre-operative talimogene laherparepvec (T-VEC) with Pembrolizumab T-VEC - intra-lesional injection into palpable lymph nodes every 3 weeks for 6 months, or until complete response of target tumors. Pembrolizumab - administered intravenously every 3 weeks for 6 months, then every 3 weeks for one year in the adjuvant setting following complete lymph node dissection. | Drug: Pembrolizumab<br>* Preoperative infusions<br>* Other names: Keytruda;Drug: Talimogene Laherparepvec<br>* Preoperative intralesional injection<br>* Other names: Imlygic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response | Pathologic response rate in the regional nodal basin assessed after complete lymph node dissection | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of Preoperative T-VEC/pembrolizumab: Adverse events and Serious Adverse Events | Adverse events and Serious Adverse Events will be collected | Every 3-6 weeks during the combination treatment period, and every 3 months after surgery through study completion, up to 5 years |