Stage IIIB MelanomaPhase 1NCT06190249
Efficacy & Safety for LN144 With Pembrolizumab With High Risk Stage IIIb-dResectable Melanoma
A Phase 1 study testing LN-144, Cyclophosphamide and Mesna in people with Stage IIIB Melanoma and Stage IIIC Melanoma, run by James Isaacs, MD.
Trial summary
The purpose of this study is to evaluate the efficacy of adjuvant adoptive cell therapy (ACT) via infusion of LN-144 (autologous TIL) followed by interleukin-2 (IL-2) after a nonmyeloablative lymphodepletion (NMA-LD) preparative regimen, followed by Pembrolizumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IIID Melanoma
- What is being tested?
- LN-144, Cyclophosphamide and Mesna
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 2 Dec 2024to Jul 2028
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have a confirmed diagnosis of resectable, Stage III, High-Risk melanoma defined by AJCC v8 as Stage IIIB, IIIC, or IIID.
- Disease must be resected to no evidence of disease on imaging and no gross disease residually with the exception of positive microscopic margin. No prior treatment with immunotherapy.
- One (1) lesion at least 1.5cm in size (solitary or aggregate) available for TIL harvesting that has not undergone prior embolization or RT in prior 3 months unless subsequent growth is demonstrated.
- Palliative radiation therapy is permitted so long as it does not involve lesions being selected for TIL. Washout is not required if all related toxicities have resolved to ≤ Grade 1 as per CTCAE v 5.0
- Previous surgical procedure(s) is/are permitted provided that wound healing has occurred, all complications have resolved, and at least 14 days have elapsed (for major operative procedures) prior to the tumor resection.
- Patients must have a washout period ≥ 21 days from prior anti-cancer therapy(ies) to the start of the planned NMA-LD pre-conditioning regimen.
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- Patients must be ≥ 18 years of age at the time of consent.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of ≥ 3 months in the opinion of the Investigator.
- Patients must have the following hematologic parameters:• Absolute neutrophil count (ANC) ≥ 1000/mm3, •Hemoglobin (Hb) ≥ 9.0 g/dL, •Platelet ≥ 100,000/mm3
- Patients must have adequate organ function: •Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal (≤ 3 × ULN); patients with liver metastasis ≤ 5 × ULN, •Estimated creatinine clearance (eCrCl) ≥ 40 mL/min using the Cockcroft-Gault formula at Screening, •Total bilirubin ≤ 2 mg/dL, •Patients with Gilbert's syndrome must have a total bilirubin ≤ 3 mg/dL
- Patients of childbearing potential (or female partners of male participants) 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 during treatment and for 12 months after their last dose of IL-2.
- Approved methods of birth control are as follows: Combined (estrogen and progesterone containing) hormonal birth control associated with inhibition of ovulation: oral, intravaginal, transdermal, Progesterone-only hormonal birth control associated with inhibition of ovulation: oral, injectable, implantable, Intrauterine device (IUD), Intrauterine hormone-releasing system (IUS), Bilateral tubal occlusion, Vasectomized partner, True sexual abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar ovulation, symptothermal, post-ovulation methods) is not acceptable
- Patients (or legally authorized representative) 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.
Who cannot join
- Patients who have received an organ allograft or prior cell transfer therapy within the past 20 years that included a non-myeloablative or myeloablative chemotherapy regimen.
- 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:
- NMA-LD preparative regimen (cyclophosphamide, mesna, and fludarabine),
- Proleukin®, aldesleukin, IL-2,
- Pembrolizumab,
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- Antibiotics (ABX) of the aminoglycoside group (i.e., streptomycin, gentamicin); except those who are skin-test negative for gentamicin hypersensitivity,
- Any component of the LN-144 infusion product formulation including dimethyl sulfoxide (DMSO), human serum albumin (HSA), IL-2, and dextran-40.
- Patients with symptomatic and/or untreated brain metastases (of any size and any number).
- Patients who are on chronic systemic steroid therapy except for those requiring steroid therapy for management of adrenal insufficiency; these patients may receive no more than 10 mg of prednisone or its equivalent daily.
- Patients who are pregnant or breastfeeding.
- 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 systems.
- Patients must have a negative syphilis assay (per local standard, e.g., rapid plasma reagin [RPR], venereal disease research laboratory [VDRL]) and be seronegative for the human immunodeficiency virus (HIV1 and HIV2 antibody titers). Patients with positive serology for hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) or hepatitis C virus (anti-HCV) indicating acute or chronic infection must have the corresponding polymerase chain reaction (PCR) assay; patients may be enrolled if the viral load by PCR is undetectable with/without active treatment. Additional serology testing may be required depending on local prevalence of certain viral exposures
- Patients who have any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease [SCID] and acquired immunodeficiency syndrome [AIDS])
- Patients who have received a live or attenuated vaccination within 28 days prior to the start of NMA-LD pre-conditioning regimen.
- Participant has an LVEF < 45% and is New York Heart Association (NYHA) Class 1. For participants ≥ 60 years of age OR who have a history of clinically relevant cardiac disease, no irreversible wall movement abnormality is demonstrated on a cardiac stress test (or equivalent local standard stress test). Participants with an abnormal cardiac stress test may be considered for study participation if they have adequate ejection fraction and cardiology clearance with approval of the Investigator.
- Patients who have obstructive or restrictive pulmonary disease and have a documented forced expiratory volume in 1 second (FEV1) of ≤ 60% of predicted normal:
- If a patient is not able to perform reliable spirometry due to abnormal upper airway anatomy (i.e., tracheostomy), a 6-minute walk test may be used to assess pulmonary function.,
- Patients who are unable to walk a distance of at least 80% predicted for age and sex or demonstrates evidence of hypoxia at any point during the test (SpO2 < 90%) are excluded.
- Patients who have had another primary malignancy within the previous three (3) years (with the exception of carcinoma in situ of the breast, cervix, or bladder; localized prostate cancer; non-melanoma skin cancer that has been adequately treated; or other cancers that in the opinion of the investigator do not place the subject at a significantly higher risk).
- Active infections, including COVID-19, within 30 days
- Participated in another clinical study with an investigational product within 21 days of the initiation of treatment.
About this study
Official title: A Phase I Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN144) With Adjuvant Pembrolizumab for Treatment of Immunotherapy Naïve Patients With High Risk Stage IIIb-dResectable Melanoma
The purpose of this study is to evaluate the efficacy of adjuvant adoptive cell therapy (ACT) via infusion of LN-144 (autologous TIL) followed by interleukin-2 (IL-2) after a nonmyeloablative lymphodepletion (NMA-LD) preparative regimen, followed by Pembrolizumab.
Read the detailed description
Primary:
- To evaluate the efficacy of LN-144 with adjuvant Pembrolizumab in Stage IIIb-d melanoma patients as assessed by 6 and 12-month relapse-free survival (RFS)
Secondary:
- To further evaluate the efficacy of LN-144 with adjuvant Pembrolizumab in Stage IIIb-d melanoma patients using overall survival (OS) and distant metastasis-free survival
- To characterize the safety profile of LN-144 in Stage IIIb-d melanoma patients as measured by the incidence of Grade ≥ 3 treatment emergent adverse events (TEAEs) within 3 months of LN-144 administration
- To identify location of relapse
- Rate of achievable recruitment for duration of planned recruitment period
- Being tested
- LN-144, Cyclophosphamide, Mesna, Fludarabine, Interleukin-2 (IL-2)
- Keywords
- Autologous Tumor Infiltrating Lymphocytes, LN144, Resectable Melanoma, Immunotherapy Naive
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LN-144Biological
Also called Autologous Tumor Infiltrating Lymphocytes (TIL)
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-144), followed by IL-2.
CyclophosphamideDrug
Also called Cytoxan
Given by IV.
MesnaDrug
Also called Mesnex
Given by IV.
FludarabineDrug
Also called Fludara
Given by IV.
Interleukin-2 (IL-2)Biological
Also called Aldesleukin, Proleukin
Given by IV.
PembrolizumabDrug
Also called Keytruda
Given by IV.
| Study group | Role | What they receive |
|---|---|---|
| LN-144 Therapy | Experimental | All patients will receive LN-144 therapy, consisting of these steps:
1. Harvest (surgical resection of tumor tissue) to provide the autologous tissue that serves as the source of LN-144.
2. Production of LN-144 investigational product (IP) at a central Good Manufacturing Practice (GMP) facility
3. A 5-day nonmyeloablative lymphodepletion (NMA-LD) preparative regimen
4. Infusion of the LN-144 product (Day 0)
5. Administration of IV interleukin-2 (IL-2) for ≤ 6 doses.
6. Infusion of pembrolizumab 200 mg (Week 12) every 3 weeks for up to 1 year (17 cycles) Receives: Biological: LN-144; Drug: Cyclophosphamide; Drug: Mesna; Drug: Fludarabine; Biological: Interleukin-2 (IL-2); Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
LN-144 Efficacy
measured as the rate of RFS (Relapse-Free Survival)
Measured: 1 year following TIL infusion
LN-144 Safety Profile
measured by the incidence Serous Adverse Events (SAE)
Measured: Within 30 days of LN-144 administration
Secondary outcomes (6)
LN-144+ Pembrolizumab Efficacy Overall Survival (OS)
measured using overall survival (OS). This is the length of time from the start of treatment to a given time point that measures participants on the study that are still alive
Measured: 1 year after initial treatment
LN-144+ Pembrolizumab Efficacy Relapse-Free Survival (RFS)
measured using Relapse-free survival described as the length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer
Measured: 1 year after initial treatment
LN-144+ Pembrolizumab Efficacy Distant Metastasis-Free Survival (DMFS)
measured using distant metastasis-free survival (DMFS). This is the length of time from the start of treatment for cancer that a patient is still alive and the cancer has not spread to other parts of the body.
Measured: 1 year after inital treatment
LN-144 Safety Profile
Incidence of adverse events following LN144 administration
Measured: within 12 months of LN144 administration
Location of relapse
In participants who relapse, the location of the relapse will be located using standard imaging and physical exam
Measured: Up to 3 years
Rate of Achievable Recruitment
The number of participants enrolled will be counted in which an "achievable" recruitment is considered to be 1 participant every 2-3 months.
Measured: 2 years from the study start date
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2024
- Study start2 Dec 2024
- Primary completionJan 2028 (estimated)
- Study completionJul 2028 (estimated)
Why it stopped: Iovance withdrew support due to length of time required to meet accrual goal.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IIIB MelanomaStudies 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- James Isaacs, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Iovance Biotherapeutics, Inc.
- Responsible party
- Sponsor-investigator, James Isaacs, MD, Case Comprehensive Cancer Center
- Investigators
- James Isaacs, MD, Principal investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06190249
- Sponsor's protocol ID
- CASE4622
- Status last verified
- Jun 2025
- First submitted
- 14 Dec 2023
- Last updated
- 5 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN144) With Adjuvant Pembrolizumab for Treatment of Immunotherapy Naïve Patients With High Risk Stage IIIb-dResectable Melanoma
- ClinicalTrials.gov ID
- NCT06190249
- Acronym / sponsor ID
- CASE4622
- Keywords
- Autologous Tumor Infiltrating Lymphocytes, LN144, Resectable Melanoma, Immunotherapy Naive
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Iovance withdrew support due to length of time required to meet accrual goal.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- James Isaacs, MDUniversity, hospital or other
- Collaborators
- Iovance Biotherapeutics, Inc.
- Study start
- 2 Dec 2024 (actual)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 5 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 purpose of this study is to evaluate the efficacy of adjuvant adoptive cell therapy (ACT) via infusion of LN-144 (autologous TIL) followed by interleukin-2 (IL-2) after a nonmyeloablative lymphodepletion (NMA-LD) preparative regimen, followed by Pembrolizumab.
Detailed description
Primary:
- To evaluate the efficacy of LN-144 with adjuvant Pembrolizumab in Stage IIIb-d melanoma patients as assessed by 6 and 12-month relapse-free survival (RFS)
Secondary:
- To further evaluate the efficacy of LN-144 with adjuvant Pembrolizumab in Stage IIIb-d melanoma patients using overall survival (OS) and distant metastasis-free survival
- To characterize the safety profile of LN-144 in Stage IIIb-d melanoma patients as measured by the incidence of Grade ≥ 3 treatment emergent adverse events (TEAEs) within 3 months of LN-144 administration
- To identify location of relapse
- Rate of achievable recruitment for duration of planned recruitment period
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LN-144 Therapy | Experimental | Biological: LN-144, Drug: Cyclophosphamide, Drug: Mesna, Drug: Fludarabine, Biological: Interleukin-2 (IL-2), Drug: PembrolizumabAll patients will receive LN-144 therapy, consisting of these steps: 1. Harvest (surgical resection of tumor tissue) to provide the autologous tissue that serves as the source of LN-144. 2. Production of LN-144 investigational product (IP) at a central Good Manufacturing Practice (GMP) facility 3. A 5-day nonmyeloablative lymphodepletion (NMA-LD) preparative regimen 4. Infusion of the LN-144 product (Day 0) 5. Administration of IV interleukin-2 (IL-2) for ≤ 6 doses. 6. Infusion of pembrolizumab 200 mg (Week 12) every 3 weeks for up to 1 year (17 cycles) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Must have a confirmed diagnosis of resectable, Stage III, High-Risk melanoma defined by AJCC v8 as Stage IIIB, IIIC, or IIID.
- Disease must be resected to no evidence of disease on imaging and no gross disease residually with the exception of positive microscopic margin. No prior treatment with immunotherapy.
- One (1) lesion at least 1.5cm in size (solitary or aggregate) available for TIL harvesting that has not undergone prior embolization or RT in prior 3 months unless subsequent growth is demonstrated.
- Palliative radiation therapy is permitted so long as it does not involve lesions being selected for TIL. Washout is not required if all related toxicities have resolved to ≤ Grade 1 as per CTCAE v 5.0
- Previous surgical procedure(s) is/are permitted provided that wound healing has occurred, all complications have resolved, and at least 14 days have elapsed (for major operative procedures) prior to the tumor resection.
Key exclusion criteria (22 listed)
- Patients who have received an organ allograft or prior cell transfer therapy within the past 20 years that included a non-myeloablative or myeloablative chemotherapy regimen.
- 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 who are on chronic systemic steroid therapy except for those requiring steroid therapy for management of adrenal insufficiency; these patients may receive no more than 10 mg of prednisone or its equivalent daily.
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 |
|---|---|---|
| LN-144Also: Autologous Tumor Infiltrating Lymphocytes (TIL)A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-144), followed by IL-2. | Biological | LN-144 Therapy |
| CyclophosphamideAlso: CytoxanGiven by IV. | Drug | LN-144 Therapy |
| MesnaAlso: MesnexGiven by IV. | Drug | LN-144 Therapy |
| FludarabineAlso: FludaraGiven by IV. | Drug | LN-144 Therapy |
| Interleukin-2 (IL-2)Also: Aldesleukin, ProleukinGiven by IV. | Biological | LN-144 Therapy |
| PembrolizumabAlso: KeytrudaGiven by IV. | Drug | LN-144 Therapy |
Primary outcome
LN-144 Efficacy
Time frame: 1 year following TIL infusion
measured as the rate of RFS (Relapse-Free Survival)
LN-144 Safety Profile
Time frame: Within 30 days of LN-144 administration
measured by the incidence Serous Adverse Events (SAE)
6 secondary outcomes
LN-144+ Pembrolizumab Efficacy Overall Survival (OS)
Time frame: 1 year after initial treatment
LN-144+ Pembrolizumab Efficacy Relapse-Free Survival (RFS)
Time frame: 1 year after initial treatment
LN-144+ Pembrolizumab Efficacy Distant Metastasis-Free Survival (DMFS)
Time frame: 1 year after inital treatment
LN-144 Safety Profile
Time frame: within 12 months of LN144 administration
Location of relapse
Time frame: Up to 3 years
Rate of Achievable Recruitment
Time frame: 2 years from the study start date
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2025.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
James Isaacs, MD principal investigator
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LN-144, Cyclophosphamide and Mesna in people with Stage IIIB Melanoma and Stage IIIC Melanoma, run by James Isaacs, MD.
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 13 inclusion and 22 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: withdrawn, as of the sponsor's last update on 5 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LN-144 Efficacy (time frame: 1 year following TIL infusion). 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 5 Jun 2025.