Talimogene Laherparepvec and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

Recurrent Melanoma Clinical Trial

Official title: A Phase II Study of Combining Talimogene Laherparepvec (T-VEC) (NSC-785349) and MK-3475 (Pembrolizumab) (NSC-776864) in Patients With Advanced Melanoma Who Have Progressed on Anti-PD1/L1 Based Therapy

Status Active, not recruiting

Clinical Trial Summary

This phase II trial studies how well talimogene laherparepvec and pembrolizumab work in treating patients with stage III-IV melanoma. Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving talimogene laherparepvec and pembrolizumab may work better in treating patients with melanoma by shrinking the tumor.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To evaluate the objective response rate (confirmed complete and partial responses) of treatment with talimogene laherparepvec (T-VEC) in combination with pembrolizumab (MK-3475) following progression on prior anti-PD-1 or anti-PD-L1 therapy alone or in combination with other agents different from talimogene laherparepvec (T-VEC).

SECONDARY OBJECTIVES:

I. To estimate the durable response rate. II. To estimate the objective response rate (ORR) defined as confirmed and unconfirmed, complete and partial responses in the injected lesions.

III. To estimate the ORR in the non-visceral, non-injected lesions. IV. To estimate the ORR in the visceral lesions (Cohort A). V. To estimate the median progression-free survival (PFS). VI. To estimate the median overall survival (OS). VII. To evaluate the toxicity of the regimen.

TRANSLATIONAL OBJECTIVES:

I. To evaluate whether adding talimogene laherparepvec (T-VEC) to PD1 blockade can increase T-cell infiltration into tumors and whether change in T-cell infiltration is associated with response.

II. To evaluate whether adding talimogene laherparepvec (T-VEC) to PD1 blockade can increase T-cell receptor (TCR) clonality in tumors and in peripheral blood and whether increased TCR clonality is associated with response.

III. To evaluate whether intra-tumoral injection of talimogene laherparepvec (T-VEC) can improve the tumor immune microenvironment.

IV. To evaluate whether tumor mutational load, mutations in the IFN pathway, and circulating tumor deoxyribonucleic acid (DNA) profile are is associated with response to talimogene laherparepvec (T-VEC) plus pembrolizumab (MK-3475) therapy in the anti-PD1/L1 therapy refractory melanoma patients.

OUTLINE:

Patients receive talimogene laherparepvec intralesionally (IL) and pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 1 year and then annually for a total of 5 years. ;

Related Conditions & MeSH terms

• Advanced Melanoma
• Melanoma
• Recurrent Melanoma
• Skin Neoplasms
• Stage III Cutaneous Melanoma AJCC v7
• Stage IIIA Cutaneous Melanoma AJCC v7
• Stage IIIB Cutaneous Melanoma AJCC v7
• Stage IIIC Cutaneous Melanoma AJCC v7
• Stage IV Cutaneous Melanoma AJCC v6 and v7
• Unresectable Melanoma

• NCT number: NCT02965716
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 5, 2018
• Completion date: November 5, 2024