Locoregional Administration of TIL and Lymphodepletion in Patients With Melanoma and Liver Metastases (HAITILS-PHP)

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Cutaneous Melanoma; Uveal Melanoma
• Intervention / Treatment: Drug: Autologous Tumor Infiltrating Lymphocytes; Drug: Melphalan; Drug: Interleukin-2

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lars Ny; Phone Number: +46 31 342 10 00; Email: lars.ny@vgregion.se
• Study Contact Backup: Name: Axel Nelson; Email: axel.nelson@vgregion.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient is willing and able to provide written informed consent and comply with study procedures. Written informed consent must be signed and dated before the start of specific protocol procedures.
• Patient must have a histologically/cytologically confirmed diagnosis of:
• stage IV uveal melanoma with or without any previous systemic therapy OR
• stage IV cutaneous melanoma with confirmed progression following at least one or two prior systemic therapies including a programmed cell death protein-1 (PD-1) inhibitor with or without a CTLA-4 inhibitor; and if BRAF V600 mutation-positive, also a BRAF inhibitor or a BRAF inhibitor in combination with a MEK inhibitor.
• Measurable disease by computed tomography (CT) per RECIST 1.1 criteria with at least one target lesion identified in the liver and where the distribution pattern of metastasis is predominantly engaging the liver as judged by the investigator.
• At least one resectable lesion in the liver (or aggregate of lesions resected) of a minimum size of 0.5 cm in diameter post- resection to generate TILs.
• ECOG performance status of 0 - 1.

Exclusion Criteria:

• Life expectancy of less than 3 months.
• Reduced renal function defined as S-Creatinine >=1.5xULN or Creatinine Clearance < 40 mL/min, calculated using the Cockroft and Gault formula.
• Reduced hepatic function (defined as ASAT, ALAT, bilirubin > 3*ULN and PK- INR > 1.5) or medical history of liver cirrhosis or portal hypertension.
• Hemoglobin <90 g/L or platelets <100x109/L or neutrophils <1.5x109/L
• Use of live vaccines four weeks before or after the start of study.
• Infection of human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), hepatitis B or hepatitis C.
• Active autoimmune disease.
• A condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Concomitant therapy with any other anti- cancer therapy, concurrent medical conditions requiring use of immunosuppressive medications or use of other investigational drugs.
• Has a known additional malignancy of other diagnosis that is progressing or requires active treatment.
• A history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous tumor infiltrating lymphocytes (TIL)	Drug: Autologous Tumor Infiltrating Lymphocytes; Administered via hepatic arterial infusion (HAI); Drug: Melphalan; Administered via isolated hepatic perfusion; Drug: Interleukin-2; low-dose, administered s.c.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events	Graded according to Common Terminology Criteria for Adverse Events version 5.0	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Defined as the proportion of patients with a best overall response of partial response or better defined by RECIST 1.1	5 years
Progression-free survival	Defined as the time from inclusion to objective tumor progression (determined by RECIST 1.1), or death due to any cause, whichever occurred first.	5 years
hepatic Progression-free survival	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.	5 years
Duration of response	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.	5 years
Overall survival	Defined as the time from inclusion to the date of death due to any cause	5 years
Evaluation of Tolerability	Defined as the proportion of patients included that receive PHP and TIL	5 years

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region

Study record dates

Study Major Dates

• Study Start (Estimated): December 31, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: June 5, 2023
• First Submitted That Met QC Criteria: June 5, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: ACT; TIL; PHP
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan; Interleukin-2
• Other Study ID Numbers: 2023-006126-32

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No