Neoadj Admin Autologous Tumor Infiltrating Lymphocytes & Pembrolizumab for Treatment of Adv Melanoma Patients

Stage IV Melanoma Clinical Trial

Official title: A Phase IB Study to Assess the Safety and Efficacy of Neoadjuvant Administration of Autologous Tumor Infiltrating Lymphocytes (LN144/Lifileucel) and Pembrolizumab for Treatment of Patients With Locally Advanced (Stage IIIB-D)/Metastatic (Stage IV) Melanoma

Status Active, not recruiting

Clinical Trial Summary

This phase I/II trial tests the safety and side effects of LN-144 (Lifileucel) and pembrolizumab in treating patients with stage IIIB-D or stage IV melanoma that has spread to nearby tissue or lymph nodes. Biological therapies, such as LN-144 (Lifileucel), use substances made from living organisms that may attack specific tumor cells and stop them from growing or kill them. 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 lifileucel and pembrolizumab may make the tumor smaller.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the feasibility of the neoadjuvant administration of Pembrolizumab and LN-144 (Lifileucel) isolated from tumor-involved metastatic lymph node(s) in 3 stage IIIB-D melanoma patients. (Part 1) II. To evaluate the safety profile and surgical tolerability of MK-3475 (pembrolizumab) and LN-144 (Lifileucel) in 12 patients, as measured by the incidence of grade >= 3 treatment-emergent adverse events (TEAEs). (Part 2)

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of Pembrolizumab and LN-144(Lifileucel) in 12 patients by determining the overall objective response rate (ORR), using the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) and immune-related RECIST (irRECIST) criteria, as assessed by the investigator. (Part 2 only) II. To further evaluate the efficacy of Pembrolizumab and LN-144 (Lifileucel) in 12 patients using the 24-month relapse-free survival rate (RFS), using RECIST 1.1 and irRECIST, as assessed by the investigator. (Part 2 only)

EXPLORATORY OBJECTIVES:

I. To determine rates of major pathologic response (MPR) for high-risk stage IIIB-D melanoma patients treated with neoadjuvant administration of MK-3475 (pembrolizumab) and LN-144 (Lifileucel).

II. To determine the association between the proportion of PD-1+CD4+ or CD8+ tumor infiltrating lymphocytes (TILs) isolated from tumor involved lymph node(s) via flow cytometry, and probability of MPR, ORR, and RFS.

III. To determine the association between neoantigen specificity and probability of MPR, ORR, and RFS.

IV. To determine the correlation between tumor mutation burden (TMB) and MPR, ORR, and RFS.

V. To determine the correlation between intratumoral IFN-gamma and T-effector gene signatures and probability of MPR, ORR, and RFS.

VI. To evaluate the correlation between serum cytokines (IL-8, IL-6), and probability of MPR, ORR, and RFS.

VII. To evaluate the success rates of growing TILs from lymph node metastases, and the potential predictive factors (i.e., patient's age, CD8/CD4 ratios, inhibitory receptor expressions).

VIII. To correlate the doses of TILs infused to patients and the probability of MPR, ORR, and RFS.

IX. To perform additional translational studies utilizing the unstained slides or FFPE (paraffin blocks) on the resected melanoma tumor specimen post LN-144 (Lifileucel) neoadjuvant therapy.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) on day -14, cyclophosphamide IV once daily (QD) on days -7 to -6, fludarabine IV over 30 minutes QD on days -5 to -1, and lifileucel IV infusion on day 0. Patients also receive pembrolizumab IV on day 28 and 70, and undergo surgery on day 80.

MAINTENANCE: Patients receive pembrolizumab IV every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 2 years. ;

Related Conditions & MeSH terms

• Locally Advanced Melanoma
• Melanoma
• Pathologic Stage IIIB Cutaneous Melanoma AJCC v8
• Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
• Pathologic Stage IIID Cutaneous Melanoma AJCC v8
• Skin Neoplasms
• Stage IV Melanoma

• NCT number: NCT05176470
• Study type: Interventional
• Source: Ohio State University Comprehensive Cancer Center
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: July 1, 2022
• Completion date: December 31, 2024