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Clinical Trial 18309

Cancer Type: Cutaneous
Interventions:Aldesleukin (Interleukin-2); IL-2 (Interleukin-2); Interleukin-2; Not Applicable; Proleukin (Interleukin-2); TIL

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Amod Sarnaik

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Phase 2, Multicenter Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN-144) for Treatment of Patients with Metastatic Melanoma

Summary

The purpose of this study is to find out if an investigational product called LN-144 is safe to give to patients with metastatic melanoma and if processing tumors to obtain cells in a central lab works. LN-144 is also called "tumor infiltrating lymphocytes" (TIL).

Objective

Primary Objectives: To assess the safety and toxicities associated with the treatment regimen. To assess the feasibility of TIL production, defined as the percentage of patients with tumor resected from which LN-144 is successfully produced (manufacture of more than 1.5 billion viable cells). Secondary Objectives: To assess the feasibility of LN-144 administration followed by IL-2 (defined as the percentage of patients with tumor resected with LN-144 subsequently infused). To evaluate the anti-tumor activity defined by best overall response rate by RECIST 1.1 in patients who receive LN-144 followed by IL-2. Exploratory Objectives: To evaluate additional measures of efficacy for up to 24 months, including: progression-free survival (PFS), overall survival (OS), duration of response, and time to response. To explore potential immune correlates of response, outcome, and toxicity of the treatment.

Inclusion Criteria

Patients must meet all of the following inclusion criteria to be eligible for participation in the study.

  • Patients with unresectable or metastatic melanoma (Stage IIIc or Stage IV)
  • Patients must have progressed following ≥ one prior systemic therapy including a programmed cell death protein-1 (PD-1) blocking antibody; and if proto-oncogene B-Raf (BRAF) V600 mutationpositive, a BRAF inhibitor or BRAF inhibitor in combination with mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor
  • Prior to study Enrollment, documentation of radiological disease progression after the most recent therapy
  • Have at least one measurable target lesion, as defined by RECIST v1.1. Lesions in previously irradiated areas (or other local therapy) should not be selected as target lesions, unless treatment was ≥ 3 months prior to Screening, and there has been demonstrated disease progression in that particular lesion. If a lesion is partially resected to generate TIL, and remains visible on the Baseline scan after surgery, then the partially resected lesion can be used for RECIST v1.1 response assessment, but only as a non-target lesion
  • At least one resectable lesion (or aggregate of lesions resected) of a minimum 1.5 cm in diameter post-resection to generate TIL; surgical removal with minimal morbidity (defined as any procedure for which expected hospitalization is ≤ 3 days)
  • At least 18 years of age at the time of consent. Enrollment of patients > 70 years of age may be allowed after consultation with the Medical Monitor
  • Adequate organ and bone marrow function. Note: Transfusions or growth factors are not allowed 28 days prior to signing the ICF and continuing through the Screening Period
  • Must have recovered from all prior therapy-related adverse events (AEs) to ≤ Grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] v4.03. Exceptions apply.
  • Must have a washout period ≥ 28 days from prior anticancer therapy(ies) to the start of the planned NMA-LD preconditioning regimen: Targeted therapy: MEK/BRAF or other targeted agent, Chemotherapy, Immunotherapy: anti-cytotoxic T lymphocyte-associated antigen, 4 (CTLA-4)/anti-PD-1, other monoclonal antibody (mAb), or vaccine. Palliative radiation therapy is permitted so long as it does not involve lesions being selected for TIL, or as target or non-target lesions. Washout is not required if all related toxicities have resolved to ≤ Grade 1 as per CTCAE v4.03
  • Patients of childbearing potential or their partners of childbearing potential must be willing to take the appropriate precaution to avoid pregnancy or fathering a child for the duration of the study and practice an approved, highly effective method of birth control (per protocol) during treatment and for 12 months after receiving the last protocol-related therapy
  • Must have the ability to understand the requirements of the study, have provided written informed consent as evidenced by signature on an ICF approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC), and agree to abide by the study restrictions and return to the site for the required assessments, including the OS Follow-up Period.

  • Exclusion Criteria

  • Patients who have been shown to be BRAF mutation positive (V600), but have not received prior systemic therapy with a BRAF inhibitor alone or a BRAF inhibitor in combination with a MEK inhibitor
  • Patients who have received an organ allograft or prior cell transfer therapy
  • Patients with melanoma of uveal/ocular origin
  • Patients who have a history of hypersensitivity to any component or excipient of LN-144 or other study drugs.
  • Patients with symptomatic and/or untreated brain metastases (of any size and any number)
  • Patients with definitively treated brain metastases may be considered for Enrollment, and must be stable for ≥ 14 days prior to beginning the NMA-LD preconditioning regimen
  • Patients who are on chronic systemic steroid therapy for any reason
  • Patients who have active medical illness(es) that would pose increased risk for study participation, including: active systemic infections requiring systemic ABX, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune system
  • Patients who have ≥ Grade 2 hemorrhage within 14 days prior to Enrollment (tumor resection)
  • Patients who are seropositive for any of the following: Human immunodeficiency virus (HIV)-1 or HIV-2 antibodies, Hepatitis B antigen (HBsAg), or hepatitis C antibody (HCV Ab); however, patients with acute or chronic hepatitis infections may be enrolled if the viral load by polymerase chain reaction (PCR) is undetectable with/without active treatment and are HCV ribonucleic (RNA) negative. Syphilis (Rapid Plasma Reagin [RPR] test or venereal disease research laboratory [VDRL] test), Cytomegalovirus (CMV) antibody titer and Epstein-Barr virus (EBV) panel indicating active infection, Positive herpes simplex virus (HSV)-1 and HSV-2 serology. Patients who are HSV immunoglobulin M (IgM) positive will need to receive appropriate treatment and become IgM negative prior to starting the NMA-LD preconditioning regimen
  • Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency disease [SCID] and acquired immunodeficiency syndrome [AIDS])
  • Patients who have a left ventricular ejection fraction (LVEF) Class 1
  • Patients ≥ 60 years of age and who have a history of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias must have a cardiac stress test. Patients with any irreversible wall movement abnormalities are excluded
  • Patients who have a documented forced expiratory volume in 1 second (FEV1) of ≤ 60% m. Patients who have had another primary malignancy within the previous 3 years (with the exception of carcinoma in situ of the breast, cervix, or bladder; localized prostate cancer; and non-melanoma skin cancer that has been adequately treated)
  • Patients who have received a live or attenuated vaccine within 28 days of beginning the NMA-LD preconditioning regimen
  • Patients who are pregnant or breastfeeding
  • Patients whose cancer requires immediate attention or who would otherwise suffer a disadvantage by participating in this trial
  • Patients protected by the following constraints: Hospitalized persons without consent or persons deprived of liberty because of a judiciary or administrative decision, Adult persons with a legal protection measure or persons who cannot express their consent, Patients in emergency situations who cannot consent to participate in the trial.