Lifileucel for Metastatic Melanoma

Overseen By Adam Schoenfeld, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Steroids

Disqualifiers: Organ allograft, Symptomatic brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3-4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called lifileucel (a type of cell therapy) for individuals with melanoma that has spread to the brain. The goal is to determine if lifileucel can help manage brain metastases in these patients. Participants must have melanoma with brain tumors that are not causing symptoms and at least one tumor that can be surgically removed. This trial is for those who have not received certain cell therapies before and do not have active health issues that could increase risks during the study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy of more than 10 mg/day, you may not be eligible to participate.

Is there any evidence suggesting that lifileucel (LN-144) is likely to be safe for humans?

Research has shown that lifileucel, a treatment for advanced melanoma, is generally well-tolerated by patients. In a study with 160 patients, lifileucel demonstrated a promising safety record. Although there were some serious events, including 12 deaths (7.5%), these patients had complex health issues that might have contributed to these outcomes.

Despite these serious events, lifileucel remains a potential option due to its benefits in treating difficult cases of melanoma. Researchers have also studied it for other cancers, such as lung cancer, where it showed promise as a one-time treatment. Discussing the risks and benefits with a healthcare provider is important for understanding your specific situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for metastatic melanoma, like immune checkpoint inhibitors and targeted therapies, aim to boost the immune response or target specific genetic mutations. But Lifileucel is different; it uses tumor-infiltrating lymphocytes (TILs) derived from the patient's own immune cells, which are expanded and reintroduced to attack the cancer. This personalized approach can potentially target a broader range of tumor antigens. Researchers are excited because this method might overcome resistance to existing therapies and offer hope for patients with limited options, especially those with melanoma brain metastases.

What evidence suggests that lifileucel might be an effective treatment for metastatic melanoma?

Research has shown that lifileucel, also known as LN-144, holds promise for treating metastatic melanoma, a type of skin cancer that spreads to other parts of the body. Studies have found that this treatment can lead to lasting improvements in patients with advanced melanoma. Lifileucel uses special immune cells taken from the patient's own tumor to help fight the cancer. Long-term data indicates that patients lived longer after receiving lifileucel. This therapy is crucial for patients with limited options after other treatments have failed. Additionally, lifileucel is already approved for treating other cancers, such as metastatic non-small cell lung cancer, supporting its potential effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Alexander Shoushtari

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with metastatic melanoma that has spread to the brain but isn't causing symptoms. They should have at least one tumor big enough to be removed and used for treatment, be in fairly good health (able to perform daily activities), and not have serious illnesses or conditions that could make participating risky.

Inclusion Criteria

I have melanoma that has spread to my brain but I don't have symptoms.

My blood counts and organ functions are within normal ranges.

I am mostly active and doctors expect me to live for at least 3 more months.

Exclusion Criteria

Pregnant or breastfeeding

Active medical illness(es) that would pose increased risk for protocol participation

I have not received a live vaccine in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Excision

Participants undergo surgical excision to generate LN-144

1 week

Treatment

Participants receive preparative NMA-LD, followed by one-time autologous TIL infusion, and a short course of high-dose IL-2

3-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Lifileucel (LN-144)

Trial Overview The study is testing Lifileucel (LN-144), a therapy using cells from the patient's own immune system, on patients with melanoma that has spread to their brains. It's an open-label trial, meaning everyone knows they're getting this specific treatment.

How Is the Trial Designed?

Group I: Participants with Melanoma Brain Metastases Experimental Treatment 1 Intervention

Participants have melanoma brain metastases who will undergo surgical excision to generate LN-144.

Lifileucel (LN-144) is already approved in United States for the following indications:

Approved in United States as AMTAGVI for:

• Unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation-positive, a BRAF inhibitor with or without a MEK inhibitor

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Iovance Biotherapeutics, Inc.

Industry Sponsor

Trials

26

Recruited

1,800+

Published Research Related to This Trial

In a phase II study involving 66 patients with advanced melanoma who had previously undergone multiple therapies, lifileucel showed an objective response rate of 36%, indicating its potential effectiveness in a challenging patient population.

The treatment resulted in a disease control rate of 80% and demonstrated durable responses, particularly in patients who were refractory to anti-PD-1 or PD-L1 therapies, highlighting its promise as a new option for those with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma. Sarnaik, AA., Hamid, O., Khushalani, NI., et al.[2022]

In a Phase 2 trial involving 153 patients with advanced melanoma who had previously progressed on immune checkpoint inhibitors, lifileucel showed an objective response rate (ORR) of 31.4%, indicating its potential effectiveness in this challenging patient population.

The treatment demonstrated durable responses, with 41.7% of patients maintaining their response for at least 18 months, and a favorable safety profile, although common severe side effects included thrombocytopenia and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study. Chesney, J., Lewis, KD., Kluger, H., et al.[2023]

In a pilot study involving 6 patients with recurrent malignant gliomas, the treatment with locally infused autologous tumor infiltrating lymphocytes (TILs) and recombinant interleukin-2 (rIL-2) was found to be safe, with no significant complications reported.

Out of the 6 patients, 3 showed a partial response and 1 achieved a complete response at long-term follow-up, suggesting potential efficacy of this immunotherapy approach, although further studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of local autologous tumor infiltrating lymphocytes for the treatment of recurrent malignant gliomas. Quattrocchi, KB., Miller, CH., Cush, S., et al.[2020]

A retrospective analysis of 21 patients with advanced cutaneous melanoma showed that nonselected autologous tumor-infiltrating lymphocytes (TILs) resulted in a high overall response rate of 67% and a complete response rate of 19%, indicating significant efficacy even in patients who had previously undergone PD-1 inhibition.

The treatment was found to be safe, with no treatment-related deaths and a median overall survival of 21.3 months, suggesting that TIL therapy could be a promising option for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical feasibility and treatment outcomes with nonselected autologous tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma. Pillai, M., Jiang, Y., Lorigan, PC., et al.[2022]

In a Phase I study involving three patients with advanced malignant melanoma, the proposed combination of chemotherapy and immunotherapy was found to be unfeasible due to significant side effects and difficulties in maintaining the planned treatment intensity.

Despite the challenges, the study suggests that combined chemo-immunotherapy could be a promising approach for treating metastatic melanoma, prompting modifications to the treatment schedule for better feasibility and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The feasibility of repetitive courses of high-dose continuous intravenous infusion interleukin-2 and subcutaneous alpha-interferon with polychemotherapy in advanced malignant melanoma. Foppoli, M., Citterio, G., Polastri, D., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02360579

NCT02360579 | Study of Lifileucel (LN-144), Autologous ... Study of Lifileucel (LN-144), Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma (LN-144). ClinicalTrials.gov ID ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00765

Long-Term Efficacy and Safety of Lifileucel Tumor ... This 5-year analysis demonstrated long-term benefit and meaningful OS with one-time lifileucel therapy, with no additional long-term safety concerns.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11294887/

Lifileucel, an Autologous Tumor-Infiltrating Lymphocyte ... Lifileucel showed potential as a one-time treatment option for patients with metastatic non-small cell lung cancer who progressed after prior immunotherapy.

4. iovance.com iovance.com/uploads/Kottschade-JADPRO-3023-publication.pdf

Tumor-Infiltrating Lymphocyte Cell Therapy for the ... Lifileucel (Amtagvi) is a tumor-derived autologous. T cell immunotherapy approved by the US Food and Drug Administration for the treatment of adult patients ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33979178/

Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy ... - PubMed Lifileucel demonstrated durable responses and addresses a major unmet need in patients with metastatic melanoma with limited treatment options after approved ...

6. iovance.com iovance.com/uploads/FINAL-SITC-2023_C-144-01-4-Year_Print-POS-2565-publication.pdf

A 4-year analysis of the C-144-01 study and fewer liver and/or brain metastases relative to the total population (Table 1). – ... JC, BG, GS, XW, and WS: Employment: Iovance ...

7. fda.gov fda.gov/media/176417/download

Package Insert - AMTAGVI Deaths. Among 160 patients with unresectable, or metastatic melanoma who initiated the AMTAGVI regimen, there were 12 deaths (7.5%), including 2 deaths ...