NCT04223648

Programmed Cell Death 1 + Selected Cell Therapy With Durvalumab (MEDI4736) and Tremelimumab in Metastatic Melanoma

A Pilot Study Using Programmed Cell Death 1 + Selected Cell Therapy With Durvalumab (MEDI4736) and Tremelimumab in Metastatic Melanoma

• Status: Withdrawn
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of this pilot study is to assess the feasibility of mobilizing PD-1+ T cells to the peripheral blood after a single treatment with tremelimumab/durvalumab in patients with treatment naïve metastatic melanoma.

Detailed description

The primary objective of this pilot study is to assess the feasibility of mobilizing programmed cell death (PD-1)+ T cells to the peripheral blood after a single treatment with tremelimumab/durvalumab in patients with treatment naïve metastatic melanoma. Secondary objectives are to evaluate the safety and clinical activity of administering a regimen of PD-1+ selected tumor infiltrating lymphocytes (TIL)/(Interleukin) IL-2, using a cell product manufactured in the Yale Advanced Cell Therapy Laboratories and assess for clinical activities in subjects with metastatic melanoma who are not responding or have progressed after receiving first-line therapy with 1 cycle of tremelimumab/durvalumab followed by 3 cycles of ipilimumab/nivolumab followed by nivolumab monotherapy as maintenance treatment. Exploratory objective are to: 1. assess the number of PD-1+ T cells in the tumor microenvironment before and after a single treatment with tremelimumab/durvalumab. 2. conduct a preliminary assessment of the TCR clonotypes present in PD1+ cluster of differentiation 8 (CD8)+ cells (4-1BB, LAG-3, TIM-3, PD-1) versus PD1-CD8+ T-cells early in the expansion cultures and compare to clonotypes late in the final product and in peripheral blood lymphocytes (PBL) 1 and 2 months post infusion. 3. assess neoantigens present in resected tumor and correlate T cell specificity for neoantigens from TIL and peripheral blood mononuclear cell (PBMC) populations stratified by PD-1 expression in these cell populations.

Conditions

• Malignant Melanoma

Interventions

Type	Name	Description
DRUG	tremelimumab/durvalumab, ipilimumab/nivolumab and nivolumab monotherapy	Subjects will receive 1 cycle of tremelimumab/durvalumab * Subjects will undergo resection to obtain tumor for generation of autologous tumor infiltrating lymphocytes (TIL) cultures and blood draw to obtain peripheral blood mononuclear cell (PBMC)s * TIL and PBMC will undergo immunoselection based on binding to an anti-programmed cell death 1 (PD-1) antibody and then will be expanded ex vivo. Subjects will receive 3 cycles of ipilimumab/nivolumab • Subjects will undergo staging with computer tomography (CT) chest/abdomen/pelvis and brain magnetic resonance imaging (MRI) or CT scan. subjects with stable disease will continue with nivolumab monotherapy; Subjects with progressive disease will proceed to cell therapy.

Timeline

• Start date: 2020-08-15
• Primary completion: 2022-02-01
• Completion: 2025-02-01
• First posted: 2020-01-10
• Last updated: 2021-11-22

Regulatory

• FDA-regulated drug study