Melanoma Stage IIIPhase 1ADP-TILIL7NCT06204991
To Evaluate the Safety and Efficacy of ADP-TILIL7 in Patients With Locally Advanced or Metastatic Melanoma
A Phase 1 study testing ADP-TILIL7, Cyclophosphamide and Fludarabine Phosphate in people with Melanoma Stage III and Melanoma Stage IV, run by Inge Marie Svane at 2 sites in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Melanoma Stage III, Melanoma Stage IV, Melanoma
- What is being tested?
- ADP-TILIL7, Cyclophosphamide and Fludarabine Phosphate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesDenmark
- Study dates
- 1 Apr 2025to 1 Apr 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All the criteria listed in the following need to be met before patient inclusion.
- 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.
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- 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)
- Alkaline phosphatase ≤ 5 times upper normal limit
- Lactate dehydrogenase ≤ 5 times upper normal limit
- Sufficient coagulation: APPT<40 and INR<1.5
- * In selected cases it can be decided to include a patient with an eGFR < 70 ml/min with the use of a reduced dose of chemotherapy.
- 9. Signed statement of consent after receiving oral and written study information 10. Willingness to participate in the planned controls and capable of handling toxicities.
- 11. Subject must receive T-cell therapy as the next therapy following tumor resection, unless bridging therapy is administered:
- Bridging therapy is discouraged. However, if in the opinion of the Investigator, the subject requires immediate therapy after tumor resection, the subject may receive bridging therapy for the period during which the subject is awaiting the manufacture of TIL-infusion product. Bridging therapy may be a continuation of the therapy the subject was receiving prior to tumor resection or may be a new therapy.
- Following this bridging therapy, the subject must adhere to the mandatory washout periods (exclusion criterion 1) and must continue to have measurable disease prior to receiving T-cell therapy.
- 12. Age and Reproductive Status:
- Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test AND must agree to use an effective method of contraception starting at the first dose of chemotherapy for at least 12 months. WOCBP must also agree to refrain from egg donation, storage, or banking during these same time periods. The following are considered safe methods of contraception:
- Hormonal anticonception (birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch)
- Intrauterine device
- Surgical sterilization
- Surgical sterilization of male partner with verification of no sperm after the procedure
- Menopause (for more than 12 months) o Male subjects must be surgically sterile or agree to use a double-barrier contraception method or abstain from sexual activity with an WOCBP starting at the first dose of chemotherapy and for 6 months thereafter. Male subjects must also agree to refrain from sperm donation, storage, or banking.
Who cannot join
- 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
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- Corticosteroids at dose equivalent > 10 mg prednisone or any other immunosuppressive therapy. 2 weeks before TR and LDC. Note: Use of topical steroids is not an exclusion
- 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.
- The following patients will be excluded because of inability to receive high dose interleukin-2:
- History of coronary revascularization
- Patients with clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, 2o or 3o heart block
- Documented FEV-1 less than or equal to 60% predicted value for patients with: A prolonged history of cigarette smoking (greater than 20 pack years), large tumor burden in the lungs or Symptoms of respiratory distress.
- Known hypersensitivity to one of the active drugs or one or more of the excipients.
- Severe medical conditions, such as severe asthma/COLD, significant cardiac disease, poorly regulated insulin dependent diabetes mellitus among others.
- Acute/chronic infection with HIV, hepatitis, syphilis among others.
- Severe allergies or previous anaphylactic reactions.
- Active autoimmune or immune-mediated disease that has not yet resolved. Subjects with the following will be eligible:
- Immune-mediated AEs secondary to immunotherapy which has resolved to ≤ Grade 1 off steroids;
- Hypothyroidism, Type I diabetes, adrenal insufficiency, or pituitary insufficiency that are stable on replacement therapy;
- Disorders such as asthma, vitiligo, psoriasis, or atopic dermatitis that are well controlled without requiring systemic immunosuppression;
- Other stable immune conditions that do not require prednisone higher than 10 mg/day or their equivalent dose for other corticosteroid agents may be acceptable with the agreement of the Sponsor.
- Pregnant women and women breastfeeding.
- Subject who, in the opinion of the Investigator, will be unlikely to fully comply with protocol requirements.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark2 sites, 2 recruiting
- Recruiting
Department of Oncology
Herlev, 2730
Inge Marie Svane, Professor, 004538683131, inge.marie.svane@regionh.dk
Cecilie Dam Vestergaard, Medical doctor, 004538686589, cecilie.dam.vestergaard@regionh.dk
- Recruiting
Department of Oncology
Herlev, 2730
Inge Marie Svane, Professor, 004538683131, inge.marie.svane@regionh.dk
Cecilie Dam Vestergaard, Medical doctor, cecilie.dam.vestergaard@regionh.dk
About this study
Official title: Phase 1 Study to Evaluate the Safety and Efficacy of TILs Transduced With IL-7 (ADP-TILIL7) in Patients With Locally Advanced or Metastatic Melanoma
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.
Read the detailed description
Synopsis:
Over the last decade treatment for malignant melanoma (MM) has seen remarkable progress particularly with checkpoint inhibitors (anti-PD-1 and anti-CTLA-4). The combination of these inhibitors has elevated the 5-year overall survival (OS) from 5 % to 50 %. However, many patients still lack a durable response.
Results from a Phase III trial, conducted in part at CCIT-DK, have illuminated the promising potential of adoptive cell therapy utilizing tumor infiltrating lymphocytes (TILs) in the treatment of malignant melnaoma. In this trial, 168 patients were randomly assigned to receive either standard anti-CTLA-4 treatment or TILs. The outcomes revealed a notably superior overall response rate (ORR) and a higher number of complete responses (CR) among those treated with TILs.
In this phase I study the investigators intend to treat 10 subjects with locally advanced or metastatic MM. Included subjects undergo surgical removal of tumor tissue for TIL manufacturing. During TIL manufacture, the investigators will genetically modify the TILs, and enable them to produce Interleukin-7 (IL-7). This modification is anticipated to confer additional functionality to the TILs enhancing their proliferation and persistence. The lentiviral vector used to integrate the IL-7 gene to the TILs is manufactured and provided by the British/American biotechnological company, Adaptimmune. The genetically modified TILs are therefore called ADP-TILIL7.
Lymphodepleting (LD) chemotherapy is administered 7 days prior to ADP-TILIL7 infusion. ADP-TILIL7 infusion is followed by high dose (HD) Interleukin (IL-2) for a maximum of 6 doses or until tolerance.
Purpose:
The primary objective of this study is to evaluate the tolerability and safety of treatment with ADP-TILIL7. The secondary objective is to assess the clinical effect of the treatment by use of the objective response rate (using RECIST 1.1). Overall survival (OS), progression-free survival (PFS), duration of response (DoR) and disease control rate (DCR) will be determined. In addition to this replication competent lentivirus (RCL) will be monitored.
Exploratory objectives are to characterize the tumor and tumor microenvironment pre- and post infusion, ex by genomic profiling of tumor tissue to investigate the mutational landscape. Furthermore, the expression of tumor-associated immunerelated markers, including markers of phenotype and frequency of tumor infiltrating blood-derived cells. The investigators want to characterize subjects' peripheral blood which includes, but is not limited to, the phenotype and funcitionality of transduced TILs and non-transduced TILs, as well as the pharmacodynamic changes in whole blood and serum pre- and post infusion, which might include gene expression, TCR/B-cell receptor repertoire, cytokines and soluble markers. All this the investigators want to explore to understand factors that can influence response or resistance to ADP-TILIL7 therapy.
Study design:
This is a phase I, First-in-human, study. Ten (10) subjects with locally advanced or metastatic MM will be included and treated at the Department of Oncology, Herlev Hospital. Subjects can be referred from other oncology centers.
Subjects will undergo a comprehensive screening process to confirm subjects' eligibility before enrollment. Included subjects will undergo surgical tumor removal for the subsequent manufacturing of TIL's. TheTIL manifacturing process is expected to take approximately 4-6 weeks. During TIL manufacture, a subset of the TILs will be transduced with genetic material encoding the production of IL-7.
Lymphodepleting chemotherapy, Cyclophosphamide and Fludarabine phosphate, will be administered for 7 days prior to ADP-TILIL7 infusion. ADP-TILIL7 infusion is followed by high-dose IL-2 for a maximum of 6 doses or until tolerance. After the end of treatment, the subjects will be followed with clinical- and imaging controls for up to 15 years.
The inclusion period is set to commence in early 2024, with the goal of enrolling all ten patients within a span of three years. The study's completion is defined as the moment when the last subject reaches and complete the 12 months follow-up visit. The study ends once all treated subjects complete 15 years of follow-up, passes away or withdraw from the study.
The study will be monitored by the Good Clinical Practice (GCP)-unit of the Capital Region of Denmark. The Danish Medicines Agency, The GCP-unit, and Adaptimmune are allowed to audit this trial.
Population:
This study targets subjects aged 18 to 75, histologically confirmed with malignant melanoma who have experienced progression following at least one line of immune checkpoint inhibitor in the advanced or metastatic setting. Eligibility is contigent on meeting specific inclusion criteria, including acceptable performance status, kidney- and liver function, and the absence of major co-morbidities. Crucially, treatment will proceed only for the subjects with successful manufacturing of TILs. Previous clinical trials have demonstrated a success rate of TIL manufacturing from malignant melanoma exceeding 90%.
Toxicity:
The amount of toxicity caused by ADP-TILIL7 is not known. The systemic treatment with IL-7 infusion has been used in treatment of several malignancies and HIV and as an adjunct to allogeneic stem cell transplantation. In these studies, IL-7 has exhibited a generally well-tolerated safety profile. At CCIT-DK investigators boast substantial experience in treating subjects with TILs that have not been genetically modified. TIL therapy has generally been well-tolerated, with most adverse events expected to be associated with chemotherapy and high-dose IL-2 treatment.
Dosing in the first three subjects will be staggered. Each subject will have safely completed a minimum observation period of 14 days from the ADP-TILIL7 infusion before lymphodepletion of the next subject commences.
Toxicity assessment, including evaluation of treatment limiting toxicity (TLTs), will be performed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The TLT observation period will be during the first 21 days following the ADP-TILIL7 infusion.
Evaluation of clinical response:
Subjects enrolled in the study will undergo comprehensive clinical evaluations during treatment and hospitalization as well as 6, 12 and 24 weeks post-treatment with ADP-TILIL7. Thereafter clinical evaluation will take place every 3 months the first two years (year 1-2), every 6 months year 3-5, followed by evaluations every 12 months year 6-15. Diagnostic imaging, preferably PET/CT scans, will be conducted before the treatment initiation, and in conjunction with the clinical evaluations, commencing 6 weeks post-TIL treatment.
Immunological response evaluation:
Blood samples for research purposes will be systematically collected at Baseline, pre- and post-TIL infusion (day 0), during IL-2 (up to a maximum 3 days), before discharge and at week 6, week 12 and the final collection 12 months post-ADP-TILIL7/progressive disease/withdrawal whichever occurs first. Blood samples for research purposes will be selectively collected, contigent upon feasibility as assessed by the investigator. Biopsies from metastatic tumor tissue will be systematically obtined at key time points: before treatment initiation, 6 weeks post-treatment and, if applicable and deemed safe, in case of disease progression.
- Conditions
- Melanoma Stage III, Melanoma Stage IV, Melanoma
- Being tested
- ADP-TILIL7, Cyclophosphamide, Fludarabine Phosphate, Proleukin
- Keywords
- adoptive cell therapy, immunetherapy, genemodified tumor infiltrating lymphocytes, IL-7
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADP-TILIL7Biological
Autologous tumor infiltrating lymphocytes genemodified (by a lentiviral vector) to produce IL-7 upon antigen engagement
CyclophosphamideDrug
Lymphodepleting Chemotherapy
Lymphodepleting Chemotherapy
ProleukinDrug
IL-2
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: ADP-TILIL7; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Drug: Proleukin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerability of the treatment
Fraction of subjects experiencing grade >/= 3 AE
Measured: 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
Measured: Through study completion, an average of 1 year
Secondary outcomes (5)
Objective response rate
Defined as the proportion of subjects who have a partial or complete response to therapy. Response evaluation criteria in solid tumors, RECIST 1.1. criterias assesed by CT scan
Measured: Until progression up to 15 years
Overall survival
Time from initiation of treatment to death
Measured: 15 years
Progression free survival
Time from initiation of treatment until first evidence of disease progression or death
Measured: Until progression or death up to 15 years
Duration of response
Time from initiation of treatment to disease progression or death in subjects who achieve complete or partial response
Measured: 15 years
Disease control rate
The percentage of subjects whose therapeutic intervention has led to a complete response, partial response or stable disease.
Measured: 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2024
- Study start1 Apr 2025
- Primary completion1 Mar 2027 (estimated)
- Study completion1 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma Stage IIIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Inge Marie Svane
- Sponsor type
- University, hospital or other
- Collaborators
- Adaptimmune
- Responsible party
- Sponsor-investigator, Inge Marie Svane, Herlev Hospital
- Investigators
- Inge Marie Svane, Prof., M.D., Study director, Study Director, CCIT-DK, Depth of Oncology, Herlev HospitalCecilie D Vestergaard, M.D., Principal investigator, Clinical research assistant, CCIT-DK, Depth of Oncology, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06204991
- Sponsor's protocol ID
- MM2319
- Acronym
- ADP-TILIL7
- Status last verified
- Aug 2025
- First submitted
- 15 Dec 2023
- Last updated
- 24 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study to Evaluate the Safety and Efficacy of TILs Transduced With IL-7 (ADP-TILIL7) in Patients With Locally Advanced or Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT06204991
- Acronym / sponsor ID
- ADP-TILIL7 / MM2319
- Conditions
- Melanoma Stage III, Melanoma Stage IV, Melanoma
- Keywords
- adoptive cell therapy, immunetherapy, genemodified tumor infiltrating lymphocytes, IL-7
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Inge Marie SvaneUniversity, hospital or other
- Collaborators
- Adaptimmune
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 1 Apr 2028 (estimated)
- First posted
- 12 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Synopsis:
Over the last decade treatment for malignant melanoma (MM) has seen remarkable progress particularly with checkpoint inhibitors (anti-PD-1 and anti-CTLA-4). The combination of these inhibitors has elevated the 5-year overall survival (OS) from 5 % to 50 %. However, many patients still lack a durable response.
Results from a Phase III trial, conducted in part at CCIT-DK, have illuminated the promising potential of adoptive cell therapy utilizing tumor infiltrating lymphocytes (TILs) in the treatment of malignant melnaoma. In this trial, 168 patients were randomly assigned to receive either standard anti-CTLA-4 treatment or TILs. The outcomes revealed a notably superior overall response rate (ORR) and a higher number of complete responses (CR) among those treated with TILs.
In this phase I study the investigators intend to treat 10 subjects with locally advanced or metastatic MM. Included subjects undergo surgical removal of tumor tissue for TIL manufacturing. During TIL manufacture, the investigators will genetically modify the TILs, and enable them to produce Interleukin-7 (IL-7). This modification is anticipated to confer additional functionality to the TILs enhancing their proliferation and persistence. The lentiviral vector used to integrate the IL-7 gene to the TILs is manufactured and provided by the British/American biotechnological company, Adaptimmune. The genetically modified TILs are therefore called ADP-TILIL7.
Lymphodepleting (LD) chemotherapy is administered 7 days prior to ADP-TILIL7 infusion. ADP-TILIL7 infusion is followed by high dose (HD) Interleukin (IL-2) for a maximum of 6 doses or until tolerance.
Purpose:
The primary objective of this study is to evaluate the tolerability and safety of treatment with ADP-TILIL7. The secondary objective is to assess the clinical effect of the treatment by use of the objective response rate (using RECIST 1.1). Overall survival (OS), progression-free survival (PFS), duration of response (DoR) and disease control rate (DCR) will be determined. In addition to this replication competent lentivirus (RCL) will be monitored.
Exploratory objectives are to characterize the tumor and tumor microenvironment pre- and post infusion, ex by genomic profiling of tumor tissue to investigate the mutational landscape. Furthermore, the expression of tumor-associated immunerelated markers, including markers of phenotype and frequency of tumor infiltrating blood-derived cells. The investigators want to characterize subjects' peripheral blood which includes, but is not limited to, the phenotype and funcitionality of transduced TILs and non-transduced TILs, as well as the pharmacodynamic changes in whole blood and serum pre- and post infusion, which might include gene expression, TCR/B-cell receptor repertoire, cytokines and soluble markers. All this the investigators want to explore to understand factors that can influence response or resistance to ADP-TILIL7 therapy.
Study design:
This is a phase I, First-in-human, study. Ten (10) subjects with locally advanced or metastatic MM will be included and treated at the Department of Oncology, Herlev Hospital. Subjects can be referred from other oncology centers.
Subjects will undergo a comprehensive screening process to confirm subjects' eligibility before enrollment. Included subjects will undergo surgical tumor removal for the subsequent manufacturing of TIL's. TheTIL manifacturing process is expected to take approximately 4-6 weeks. During TIL manufacture, a subset of the TILs will be transduced with genetic material encoding the production of IL-7.
Lymphodepleting chemotherapy, Cyclophosphamide and Fludarabine phosphate, will be administered for 7 days prior to ADP-TILIL7 infusion. ADP-TILIL7 infusion is followed by high-dose IL-2 for a maximum of 6 doses or until tolerance. After the end of treatment, the subjects will be followed with clinical- and imaging controls for up to 15 years.
The inclusion period is set to commence in early 2024, with the goal of enrolling all ten patients within a span of three years. The study's completion is defined as the moment when the last subject reaches and complete the 12 months follow-up visit. The study ends once all treated subjects complete 15 years of follow-up, passes away or withdraw from the study.
The study will be monitored by the Good Clinical Practice (GCP)-unit of the Capital Region of Denmark. The Danish Medicines Agency, The GCP-unit, and Adaptimmune are allowed to audit this trial.
Population:
This study targets subjects aged 18 to 75, histologically confirmed with malignant melanoma who have experienced progression following at least one line of immune checkpoint inhibitor in the advanced or metastatic setting. Eligibility is contigent on meeting specific inclusion criteria, including acceptable performance status, kidney- and liver function, and the absence of major co-morbidities. Crucially, treatment will proceed only for the subjects with successful manufacturing of TILs. Previous clinical trials have demonstrated a success rate of TIL manufacturing from malignant melanoma exceeding 90%.
Toxicity:
The amount of toxicity caused by ADP-TILIL7 is not known. The systemic treatment with IL-7 infusion has been used in treatment of several malignancies and HIV and as an adjunct to allogeneic stem cell transplantation. In these studies, IL-7 has exhibited a generally well-tolerated safety profile. At CCIT-DK investigators boast substantial experience in treating subjects with TILs that have not been genetically modified. TIL therapy has generally been well-tolerated, with most adverse events expected to be associated with chemotherapy and high-dose IL-2 treatment.
Dosing in the first three subjects will be staggered. Each subject will have safely completed a minimum observation period of 14 days from the ADP-TILIL7 infusion before lymphodepletion of the next subject commences.
Toxicity assessment, including evaluation of treatment limiting toxicity (TLTs), will be performed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The TLT observation period will be during the first 21 days following the ADP-TILIL7 infusion.
Evaluation of clinical response:
Subjects enrolled in the study will undergo comprehensive clinical evaluations during treatment and hospitalization as well as 6, 12 and 24 weeks post-treatment with ADP-TILIL7. Thereafter clinical evaluation will take place every 3 months the first two years (year 1-2), every 6 months year 3-5, followed by evaluations every 12 months year 6-15. Diagnostic imaging, preferably PET/CT scans, will be conducted before the treatment initiation, and in conjunction with the clinical evaluations, commencing 6 weeks post-TIL treatment.
Immunological response evaluation:
Blood samples for research purposes will be systematically collected at Baseline, pre- and post-TIL infusion (day 0), during IL-2 (up to a maximum 3 days), before discharge and at week 6, week 12 and the final collection 12 months post-ADP-TILIL7/progressive disease/withdrawal whichever occurs first. Blood samples for research purposes will be selectively collected, contigent upon feasibility as assessed by the investigator. Biopsies from metastatic tumor tissue will be systematically obtined at key time points: before treatment initiation, 6 weeks post-treatment and, if applicable and deemed safe, in case of disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tumor-infiltrating lymphocytes genemodified with IL-7 gene for IL-7 production upon Ag engagement | Experimental | Biological: ADP-TILIL7, Drug: Cyclophosphamide, Drug: Fludarabine Phosphate, Drug: ProleukinTumor-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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- All the criteria listed in the following need to be met before patient inclusion.
- * In selected cases it can be decided to include a patient with an eGFR < 70 ml/min with the use of a reduced dose of chemotherapy.
- 9. Signed statement of consent after receiving oral and written study information 10. Willingness to participate in the planned controls and capable of handling toxicities.
- 11. Subject must receive T-cell therapy as the next therapy following tumor resection, unless bridging therapy is administered:
- Hormonal anticonception (birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch)
Key exclusion criteria (31 listed)
- Patients will be excluded if they meet one of the criteria's listed below
- Subjects with Grade 2 toxicities who are deemed stable or irreversible (e.g., peripheral neuropathy) can be enrolled.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADP-TILIL7Autologous tumor infiltrating lymphocytes genemodified (by a lentiviral vector) to produce IL-7 upon antigen engagement | Biological | Tumor-infiltrating lymphocytes genemodified with IL-7 gene for IL-7 production upon Ag engagement |
| CyclophosphamideLymphodepleting Chemotherapy | Drug | Tumor-infiltrating lymphocytes genemodified with IL-7 gene for IL-7 production upon Ag engagement |
| Fludarabine PhosphateLymphodepleting Chemotherapy | Drug | Tumor-infiltrating lymphocytes genemodified with IL-7 gene for IL-7 production upon Ag engagement |
| ProleukinIL-2 | Drug | Tumor-infiltrating lymphocytes genemodified with IL-7 gene for IL-7 production upon Ag engagement |
Primary outcome
Tolerability of the treatment
Time frame: Through study completion, an average of 1 year
Fraction of subjects experiencing grade >/= 3 AE
Feasibility of the treatment
Time frame: Through study completion, an average of 1 year
Measured by the number of subjects who undergo surgery and succesfully undergo ADP-TILIL7-infusion
5 secondary outcomes
Objective response rate
Time frame: Until progression up to 15 years
Overall survival
Time frame: 15 years
Progression free survival
Time frame: Until progression or death up to 15 years
Duration of response
Time frame: 15 years
Disease control rate
Time frame: 15 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Inge Marie Svane, Prof., M.D. study director
Study Director, CCIT-DK, Depth of Oncology, Herlev Hospital
Cecilie D Vestergaard, M.D. principal investigator
Clinical research assistant, CCIT-DK, Depth of Oncology, Herlev Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ADP-TILIL7, Cyclophosphamide and Fludarabine Phosphate in people with Melanoma Stage III and Melanoma Stage IV, run by Inge Marie Svane at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Inge Marie Svane, Prof., M.D (38683868, inge.marie.svane@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tolerability of the treatment (time frame: Through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2025.