Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Anti-Infective Agents

Analgesics

Antibodies

Antibodies, Monoclonal

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Pembrolizumab

Aldesleukin

Immunomodulating Agents

Immunoglobulins

Muromonab-CD3

Interleukin-2

Mesna

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

All patients will receive LN-144 therapy, consisting of these steps:

1. Harvest (surgical resection of tumor tissue) to provide the autologous tissue that serves as the source of LN-144.
2. Production of LN-144 investigational product (IP) at a central Good Manufacturing Practice (GMP) facility
3. A 5-day nonmyeloablative lymphodepletion (NMA-LD) preparative regimen
4. Infusion of the LN-144 product (Day 0)
5. Administration of IV interleukin-2 (IL-2) for ≤ 6 doses.
6. Infusion of pembrolizumab 200 mg (Week 12) every 3 weeks for up to 1 year (17 cycles)

LN-144 is composed of autologous TIL, which are obtained from an individual participant's tumor and expanded ex vivo through cell culture in the presence of the cytokine IL-2 and muromonab CD3, a monoclonal antibody (mAb) to human CD3 (OKT3). Participants will be given LN-144 on day 0 of the study.

LN-144

60 mg/kg of cyclophosphamide will be given intravenously to participants on days -5 and -4 of the study as a part of the NMA-LD regimen

a total of 78 mg/kg Mesna will be given to participants on days -5 and -4 of the study to prevent hemorrhagic cystitis that can be caused by the cyclophosphamide used in the NMA-LD regimen

25 mg/m2 of fludarabine will be given intravenously to participants on days -5 through -1 of the study as a part of the NMA-LD regimen

IL-2 IV administrations at a dose of 600,000 IU/kg may begin as soon as 3 hours after, but no later than 24 hours after, completion of the LN-144 infusion on Day 0. Additional IL-2 doses will be given approximately every 8 to 12 hours for up to 6 total doses

Interleukin-2 (IL-2)

Up to 17 cycles of Pembrolizumab 200mg every 3 weeks starting at Week 12 will occur for up to 1 year during the post-treatment efficacy follow-up

James Isaacs, MD

The purpose of this study is to evaluate the efficacy of adjuvant adoptive cell therapy (ACT) via infusion of LN-144 (autologous TIL) followed by interleukin-2 (IL-2) after a nonmyeloablative lymphodepletion (NMA-LD) preparative regimen, followed by Pembrolizumab.

Primary:

• To evaluate the efficacy of LN-144 with adjuvant Pembrolizumab in Stage IIIb-d melanoma patients as assessed by 6 and 12-month relapse-free survival (RFS)

Secondary:

* To further evaluate the efficacy of LN-144 with adjuvant Pembrolizumab in Stage IIIb-d melanoma patients using overall survival (OS) and distant metastasis-free survival
* To characterize the safety profile of LN-144 in Stage IIIb-d melanoma patients as measured by the incidence of Grade ≥ 3 treatment emergent adverse events (TEAEs) within 3 months of LN-144 administration
* To identify location of relapse
* Rate of achievable recruitment for duration of planned recruitment period

Efficacy & Safety for LN144 With Pembrolizumab With High Risk Stage IIIb-dResectable Melanoma

A Phase I Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN144) With Adjuvant Pembrolizumab for Treatment of Immunotherapy Naïve Patients With High Risk Stage IIIb-dResectable Melanoma

measured as the rate of RFS (Relapse-Free Survival)

measured by the incidence Serous Adverse Events (SAE)

measured using overall survival (OS). This is the length of time from the start of treatment to a given time point that measures participants on the study that are still alive

measured using Relapse-free survival described as the length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer

measured using distant metastasis-free survival (DMFS). This is the length of time from the start of treatment for cancer that a patient is still alive and the cancer has not spread to other parts of the body.

Incidence of adverse events following LN144 administration

In participants who relapse, the location of the relapse will be located using standard imaging and physical exam

The number of participants enrolled will be counted in which an "achievable" recruitment is considered to be 1 participant every 2-3 months.

Symptoms and General Pathology

Neoplasm Metastasis

Melanoma, Cutaneous Malignant

Intraocular Melanoma

Hematinics

Melphalan

Liver Extracts

Autologous TIL administered via hepatic arterial infusion followed by low dose Interleukin-2 after preconditioning chemotherapy with Melphalan.

Administered via hepatic arterial infusion

Autologous Tumor Infiltrating Lymphocytes

Melphalan will be administered once as an intravenous infusion.

After TIL infusion, Interleukin-2 will be administered subcutaneously once daily for up to 14 days.

Lars Ny

Axel Nelson

The purpose of this study is to evaluate the feasibility, safety and tolerability of treatment with autologous tumor infiltrating lymphocytes (TIL) administered via hepatic arterial infusion in patients with liver metastases (including but not restricted to) of malignant melanoma.

Hepatic Arterial Infusion of Autologous Tumor Infiltrating Lymphocytes in Patients With Melanoma and Liver Metastases

A Phase I Study Using Hepatic Arterial Infusion of Autologous Tumor Infiltrating Lymphocytes in Patients With Melanoma and Liver Metastases

Adverse events are graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

Evaluation of hepatic progression-free survival

Defined as the proportion of patients included that receive treatment with the TIL product.

Miltenyi Biomedicine GmbH

Vastra Gotaland Region

Digestive System Diseases

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Post-NMA lymphodepletion, patients are infused with their autologous TIL followed by IL-2 administration.

Fresh tumor samples will be resected from enrolled patients. Autologous TILs will be extracted and reinfused to corresponding patients after ex vivo stimulation, activation, and extensive expansion.

Tong Yuan

Tian Xia

Zhiyong Huang

Single-arm, open-label, interventional study evaluating adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) infusion followed by IL-2 after a non-myeloablative(NMA) lymphodepletion preparative regimen for the treatment of patients with advanced liver cancer.

This is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing process for the treatment of patients with advanced liver cancer. The cell transfer therapy used in this study involves patients receiving a non-myeloablative lymphodepletion preparative regimen, followed by i.v. infusion of autologous tumor-infiltrating lymphocytes followed by the administration of a regimen of IL-2.

Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Advanced Liver Cancer

Dose-limiting toxicity (DLT) will be collected and graded according to CTCAE v5.0

AE will be collected and graded according to CTCAE v5.0

Evaluate the maximum tolerated dose of TILs in patients with advanced liver cancer

PFS will be calculated as the time from TIL infusion to disease progression or death from any cause (whichever occurs first) (RECIST v1.1).

DCR will be calculated as the percentage of patients who achieved Stable Disease(SD) or better for more than 8 weeks (RECIST v1.1).

ORR will be calculated as the percentage of patients who achieved partial response (PR) or better (RECIST v1.1).

Time from TIL infusion to time of death due to any cause

Wuhan Elongevity Technology Co., Ltd.

Professor

Administered via hepatic arterial infusion (HAI)

Administered via isolated hepatic perfusion

Evaluate the safety and tolerability of treatment with autologous tumor infiltrating lymphocytes (TIL) administered via hepatic arterial infusion and preconditioning with percutaneous hepatic perfusion in patients with liver metastases (but not restricted to) of malignant melanoma

Locoregional Administration of TIL and Lymphodepletion in Patients With Melanoma and Liver Metastases

Hepatic Arterial Infusion of Autologous Tumor Infiltrating Lymphocytes Preconditioned With Percutaneous Hepatic Perfusion With Melphalan in Patients With Melanoma and Liver Metastases

Graded according to Common Terminology Criteria for Adverse Events version 5.0

Defined as the proportion of patients with a best overall response of partial response or better defined by RECIST 1.1

Defined as the time from inclusion to objective tumor progression (determined by RECIST 1.1), or death due to any cause, whichever occurred first.

Defined as the time from inclusion to objective tumor progression in the liver (determined by RECIST 1.1), or death due to any cause, whichever occurred first.

Defined as the time from the first documented response and the date of the first documented tumor progression, death, or the last tumor assessment that occurred before subsequent therapy.

Defined as the time from inclusion to the date of death due to any cause

Defined as the proportion of patients included that receive PHP and TIL

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy & Safety for LN144 With Pembrolizumab With High Risk Stage IIIb-dResectable Melanoma	NCT06190249	Stage IIIB Mela... Stage IIIC Mela... Stage IIID Mela...	LN-144 Cyclophosphamid... Mesna Fludarabine Interleukin-2 (... Pembrolizumab	18 Years -	Case Comprehensive Cancer Center
Hepatic Arterial Infusion of Autologous Tumor Infiltrating Lymphocytes in Patients With Melanoma and Liver Metastases	NCT04812470	Metastatic Uvea... Metastatic Cuta...	Autologous Tumo... Melphalan Interleukin-2	18 Years -	Vastra Gotaland Region
Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Advanced Liver Cancer	NCT06084299	Liver Cancer	Autologous Tumo...	18 Years - 70 Years	Tongji Hospital
Locoregional Administration of TIL and Lymphodepletion in Patients With Melanoma and Liver Metastases	NCT05903937	Uveal Melanoma Metastatic Cuta...	Autologous Tumo... Melphalan Interleukin-2	18 Years -	Vastra Gotaland Region
Efficacy & Safety for LN144 With Pembrolizumab With High Risk Stage IIIb-dResectable Melanoma	NCT06190249	Stage IIIB Mela... Stage IIIC Mela... Stage IIID Mela...	LN-144 Cyclophosphamid... Mesna Fludarabine Interleukin-2 (... Pembrolizumab	18 Years -	Case Comprehensive Cancer Center
Hepatic Arterial Infusion of Autologous Tumor Infiltrating Lymphocytes in Patients With Melanoma and Liver Metastases	NCT04812470	Metastatic Uvea... Metastatic Cuta...	Autologous Tumo... Melphalan Interleukin-2	18 Years -	Vastra Gotaland Region

Spots Global Cancer Trial Database for autologous tumor infiltrating lymphocytes