Actively Recruiting

Phase 1
Age: 18Years - 75Years
All Genders
NCT06204991

To Evaluate the Safety and Efficacy of ADP-TILIL7 in Patients With Locally Advanced or Metastatic Melanoma

Led by Inge Marie Svane · Updated on 2025-08-24

10

Participants Needed

2

Research Sites

156 weeks

Total Duration

On this page

Sponsors

I

Inge Marie Svane

Lead Sponsor

A

Adaptimmune

Collaborating Sponsor

AI-Summary

What this Trial Is About

The primary objective of this Phase 1 clinical trial is to evaluate the feasibility and tolerability of a novel generation of gene-modified tumor infiltrating lymphocytes (TILs) in a cohort of 10 patients aged 18-75 diagnosed with unresectable or metastatic melanoma. TILs will undergo transduction with the Interleukin-7 (IL-7) gene, for IL-7 production upon antigen engagement. Participants will undergo: * screening * tumor operation following autologous TIL production (incl. transduction) - takes approximately 4-6 weeks * admission for lymphodepleting chemotherapy (Cyclophosphamide and Fludarabine phosphate), TIL infusion and high-dose IL-2 infusions for a maximum of 6 doses * Following treatment, patients will undergo systematic and regularly planned assessments, encompassing clinical evaluation, biochemistry analyses, and PET/CT scans. This thorough follow-up regimen will be continued until any of the following events occur: progressive disease, withdrawal from study, or end of study, which spans a duration of 15 years for trials involving genetically modified organisms.

CONDITIONS

Official Title

To Evaluate the Safety and Efficacy of ADP-TILIL7 in Patients With Locally Advanced or Metastatic Melanoma

Who Can Participate

Age: 18Years - 75Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Histologically confirmed inoperable or metastatic melanoma (stage IIIc or IV)
  • Progressive disease after standard treatment with PD-1 checkpoint inhibition or combination with CTLA-4 checkpoint inhibition
  • Age between 18 and 75 years at time of informed consent
  • ECOG performance status of 1 or less
  • Fit for tumor resection with at least one lesion larger than 1 cm3 available for surgical removal to produce TILs
  • At least one measurable tumor parameter according to RECIST 1.1 criteria (excluding lesion to be resected)
  • Left ventricular ejection fraction (LVEF) of 50% or higher by echocardiography or MUGA scan
  • Adequate organ function including: neutrophil count ≥1500/µl, white blood cell count above lower normal limit, platelets between 100,000 and 700,000/µl, hemoglobin ≥6.0 mmol/l, estimated glomerular filtration rate (eGFR) >70 ml/min (exceptions with reduced chemotherapy dose allowed), bilirubin ≤1.5 times upper normal limit (up to 2.5 times if liver metastasis present), liver enzymes (ASAT/ALAT) ≤2.5 times upper normal limit (up to 5 times if liver metastasis), alkaline phosphatase ≤5 times upper normal limit, lactate dehydrogenase ≤5 times upper normal limit, coagulation within limits (APTT<40 and INR<1.5)
  • Signed informed consent after oral and written study information
  • Willingness and ability to participate in planned controls and manage toxicities
  • T-cell therapy as next treatment after tumor resection unless bridging therapy is necessary (bridging therapy discouraged but allowed under investigator approval with mandatory washout and measurable disease before T-cell therapy)
  • Women of childbearing potential must have negative pregnancy test and agree to effective contraception for at least 12 months starting at first chemotherapy dose; male subjects must be surgically sterile or use double-barrier contraception or abstain from sexual activity with women of childbearing potential for 6 months after first chemotherapy dose
Not Eligible

You will not qualify if you...

  • Recent cytotoxic chemotherapy within 3 weeks before tumor resection and lymphodepleting chemotherapy
  • Recent small molecule/tyrosine kinase inhibitor therapy within 1 week before tumor resection and lymphodepleting chemotherapy
  • Recent immune therapy within 2 weeks before tumor resection and lymphodepleting chemotherapy
  • Prior T-cell therapy including gene therapy with integrating vectors
  • Corticosteroids over 10 mg prednisone equivalent or immunosuppressive therapy within 2 weeks before tumor resection and lymphodepleting chemotherapy (topical steroids allowed)
  • Investigational treatment within 4 weeks or 5 half-lives before tumor resection and lymphodepleting chemotherapy
  • Radiation to pelvis or multiple bones covering ≥25% of bone marrow within 4 weeks before tumor resection and lymphodepleting chemotherapy
  • Whole brain radiotherapy or stereotactic radiosurgery within 4 weeks before tumor resection and lymphodepleting chemotherapy
  • Radiotherapy to target lesions within 3 months prior to TIL infusion unless lesion shows progression post-radiotherapy
  • History of other malignancies unless disease-free for at least 2 years (except certain treated breast and skin cancers)
  • Metastatic ocular, mucosal, or non-cutaneous melanoma (unknown primary melanoma allowed)
  • Toxicity from prior anticancer therapy not resolved to grade 1 or baseline except stable grade 2 toxicities
  • More than 2 CNS metastases or symptomatic CNS lesions larger than 1 cm with edema unless treated and stable for at least 2 months
  • History of coronary revascularization or significant heart arrhythmias
  • Lung function (FEV-1) ≤60% predicted with risk factors or symptoms
  • Known allergy to study drugs or excipients
  • Severe medical conditions such as asthma/COLD, cardiac disease, poorly regulated insulin-dependent diabetes
  • Acute or chronic infections including HIV, hepatitis, syphilis
  • Severe allergies or previous anaphylaxis
  • Active autoimmune or immune-mediated diseases not resolved to grade 1 off steroids except certain stable conditions
  • Pregnant or breastfeeding women
  • Inability to comply with study protocol as judged by investigator

AI-Screening

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Trial Site Locations

Total: 2 locations

1

Department of Oncology

Herlev, Denmark, 2730

Actively Recruiting

2

Department of Oncology

Herlev, Denmark, 2730

Actively Recruiting

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Research Team

I

Inge Marie Svane, Prof., M.D

CONTACT

C

Cecilie Vestergaard, M.D

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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