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

NCT06204991 | Recruiting Phase 1

• 1 other identifier: MM2319
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

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

Melanoma Stage III; Melanoma Stage IV; Melanoma

Keywords

adoptive cell therapy; immunetherapy; genemodified tumor infiltrating lymphocytes; IL-7

Outcome Measures

Primary Outcomes (2)

• Tolerability of the treatment

  Fraction of subjects experiencing grade \>/= 3 AE

  Through study completion, an average of 1 year

• Feasibility of the treatment

  Measured by the number of subjects who undergo surgery and succesfully undergo ADP-TILIL7-infusion

  Through study completion, an average of 1 year

Secondary Outcomes (5)

• Objective response rate

  Until progression up to 15 years

• Overall survival

  15 years

• Progression free survival

  Until progression or death up to 15 years

• Duration of response

  15 years

• Disease control rate

  15 years

Study Arms (1)

Tumor-infiltrating lymphocytes genemodified with IL-7 gene for IL-7 production upon Ag engagement

EXPERIMENTAL

Tumor-infiltrating lymphocytes grown ex-vivo from resected tumor tissue and reapplied to the patient via an intravenous infusion. Drug: Cyclophosphamide: 2 doses (69 mg/kg) prior to infusion Drug: Fludarabinephosphat 5 doses (25 mg/m2, max. 50 mg) prior to infusion Drug: Proleukin 600.000 IU/kg/dose IL-2 a maximum of 6 doses

Biological: ADP-TILIL7; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Drug: Proleukin

Interventions

ADP-TILIL7 BIOLOGICAL

Autologous tumor infiltrating lymphocytes genemodified (by a lentiviral vector) to produce IL-7 upon antigen engagement

Tumor-infiltrating lymphocytes genemodified with IL-7 gene for IL-7 production upon Ag engagement

Cyclophosphamide DRUG

Lymphodepleting Chemotherapy

Tumor-infiltrating lymphocytes genemodified with IL-7 gene for IL-7 production upon Ag engagement

Fludarabine Phosphate DRUG

Lymphodepleting Chemotherapy

Tumor-infiltrating lymphocytes genemodified with IL-7 gene for IL-7 production upon Ag engagement

Proleukin DRUG

IL-2

Tumor-infiltrating lymphocytes genemodified with IL-7 gene for IL-7 production upon Ag engagement

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed inoperable or metastatic melanoma (stage IIIc or IV).
• Progressive disease after standard treatment with PD-1 check-point inhibition or combination of aforementioned with CTLA-4 check-point inhibition.
• Age: 18 - 75 years at time of signed Informed consent.
• ECOG performance status of ≤ 1 (Appendix 2).
• Is fit for tumor resection and has at least one lesion (\> 1 cm3) available for surgical resection for manufacture of TIL.
• At least one measurable parameter in accordance with RECIST 1.1 -criteria (excluding lesion to be resected).
• LVEF assessment with documented LVEF ≥50% by either TTE (transthoracic echocardiography) or MUGA (multigated acquisition scan).
• Sufficient organ function, including:
• Absolute neutrophil count (ANC) ≥ 1.500 /µl
• Leucocyte count ≥ lower normal limit
• Platelets ≥ 100.000 /µl and \<700.000 /µl
• Hemoglobin ≥ 6.0 mmol/l
• eGFR \> 70 ml/min\*
• S-bilirubin ≤ 1.5 times upper normal limit (Exception: Subjects with liver metastasis ≤ 2.5 × ULN)
• ASAT/ALAT ≤ 2.5 times upper normal limit (Exception: Subjects with liver metastasis ≤ 5.0 × ULN)

You may not qualify if:

• Patients will be excluded if they meet one of the criteria's listed below
• Subject has received or plans to receive the following therapy/treatment prior to tumor resection (TR) or lymphodepleting chemotherapy (LDC):
• Cytotoxic chemotherapy: Washout period 3 weeks before TR and LDC
• Small molecules/TKI: Washout period 1 week before TR and LDC
• Immune therapy (monoclonal AB therapy, CPI and biologics): 2 weeks before TR and LDC
• Prior T-cell therapy, including gene therapy using an integrating vector
• Investigational treatment: 4 weeks or 5 half-lives, whichever is shorter before TR and LDC
• Radiation to the pelvis and/or multiple bones containing ≥ 25% of bone marrow: 4 weeks before TR and LDC
• Whole brain radiotherapy or brain stereotactic radiosurgery: 4 weeks before TR and LDC
• Radiotherapy to the target lesions: 3 months prior to TIL-infusion. A lesion with unequivocal progression post-radiotherapy may be considered a target lesion.
• A history of prior malignancies. Patients treated for another malignancy can participate if they are without signs of disease for a minimum of 2 years after treatment. Subjects with curatively treated ductal carcinoma in situ (DCIS or LCIS) breast cancer for which they are taking hormonal therapy is acceptable. Resectable squamous or basal cell carcinoma of the skin is acceptable.
• Patients with metastatic ocular/mucosal or other non-cutaneous melanoma. Unknown primary melanoma is eligible.
• Toxicity from previous anti-cancer therapy must have resolved to ≤ Grade 1 or baseline prior to enrollment (except for non-clinically significant toxicities e.g., alopecia, vitiligo).
• Subjects with Grade 2 toxicities who are deemed stable or irreversible (e.g., peripheral neuropathy) can be enrolled.
• Patients who have more than 2 CNS metastases or who have any CNS lesion that is symptomatic, greater than 1 cm in diameter or show significant surrounding edema on MRI scan will not be eligible until they have been treated and demonstrated no clincal or radiologic CNS progression for at least 2 months.

Sponsors & Collaborators

• Inge Marie Svane: lead
• Adaptimmune: collaborator

Study Sites (2)

Department of Oncology

Herlev, 2730, Denmark

RECRUITING

Department of Oncology

Herlev, 2730, Denmark

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

Cyclophosphamide; fludarabine phosphate; aldesleukin

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Inge Marie Svane, Prof., M.D.

  Study Director, CCIT-DK, Depth of Oncology, Herlev Hospital

  STUDY DIRECTOR

• Cecilie D Vestergaard, M.D.

  Clinical research assistant, CCIT-DK, Depth of Oncology, Herlev Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Inge Marie Svane, Prof., M.D

CONTACT

38683868; inge.marie.svane@regionh.dk

Cecilie Vestergaard, M.D

CONTACT

38686589; cecilie.dam.vestergaard@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, M.D., Ph.D.

Study Record Dates

• First Submitted: December 15, 2023
• First Posted: January 12, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: August 24, 2025

Record last verified: 2025-08

Locations

DK (2)