Neoadjuvant Combination Immunotherapy for Stage III Melanoma

• ClinicalTrials.gov Identifier: NCT03842943
• Recruitment Status: Recruiting
• First Posted: February 15, 2019
• Last Update Posted: July 19, 2022
• Sponsor: University of Louisville
• Information provided by (Responsible Party): Michael Egger, University of Louisville

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cutaneous Melanoma	Drug: Pembrolizumab; Drug: Talimogene Laherparepvec	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Neoadjuvant Combination Immunotherapy for Stage III Melanoma
• Actual Study Start Date: July 3, 2019
• Estimated Primary Completion Date: June 1, 2024
• Estimated Study Completion Date: June 1, 2027

Arms and Interventions

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 Name: Keytruda; Drug: Talimogene Laherparepvec; Preoperative intralesional injection; Other Names: T-VEC; Imlygic

Outcome Measures

Primary Outcome Measures :

1. Pathologic Complete Response [ Time Frame: 6 months ]
   Pathologic response rate in the regional nodal basin assessed after complete lymph node dissection

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Michael Egger, MD; 502-629-6950; michael.egger@louisville.edu

Locations

United States, Kentucky

University of Louisville; Recruiting

Louisville, Kentucky, United States, 40202

Contact: Stacy Baum 502-562-4370 mary.baum@louisville.edu

Sponsors and Collaborators

University of Louisville

Investigators

• Principal Investigator: Michael Egger, MD; University of Louisville

More Information

• Responsible Party: Michael Egger, Principal Investigator, University of Louisville
• ClinicalTrials.gov Identifier: NCT03842943
• Other Study ID Numbers: 181095
• First Posted: February 15, 2019
• Last Update Posted: July 19, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Pembrolizumab; Talimogene laherparepvec; Antineoplastic Agents, Immunological; Antineoplastic Agents