Neoadjuvant Combination Immunotherapy for Stage III Melanoma

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.

Study Overview

• Status: Recruiting
• Conditions: Cutaneous Melanoma
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Talimogene Laherparepvec

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 28
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael Egger, MD; Phone Number: 502-629-6950; Email: michael.egger@louisville.edu

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University of Louisville
      • Contact: Stacy Baum; Phone Number: 502-562-4370; Email: mary.baum@louisville.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combination T-VEC/Pembrolizumab; 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; Preoperative infusions; Other Names: Keytruda; Drug: Talimogene Laherparepvec; Preoperative intralesional injection; Other Names: T-VEC; Imlygic

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Louisville
• Investigators: Principal Investigator: Michael Egger, MD, University of Louisville

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2019
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2027

Study Registration Dates

• First Submitted: February 7, 2019
• First Submitted That Met QC Criteria: February 14, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): July 19, 2022
• Last Update Submitted That Met QC Criteria: July 16, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab; Talimogene laherparepvec
• Other Study ID Numbers: 181095

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes