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

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open label study evaluating lifileucel (LN-144) in patients with melanoma brain metastases.

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.

What data supports the effectiveness of the treatment Lifileucel for metastatic melanoma?

Research shows that Lifileucel, a treatment using a patient's own immune cells, had a 36% response rate in patients with advanced melanoma who had not responded to other treatments. This suggests it can be effective for those with limited options. ^{1 2 3 4 5}

Is Lifileucel safe for humans?

Lifileucel, a treatment using a patient's own immune cells, has been tested in people with advanced melanoma and showed no treatment-related deaths. Some patients experienced side effects related to the preparation and infusion process, but these were generally consistent with other similar treatments. ^{2 3 6 7 8}

How is the treatment Lifileucel different from other treatments for metastatic melanoma?

Lifileucel is unique because it uses a patient's own immune cells, called tumor-infiltrating lymphocytes (TILs), which are collected, grown in large numbers in a lab, and then infused back into the patient to help fight the cancer. This approach is different from standard treatments like chemotherapy or targeted therapies, as it directly harnesses the body's immune system to target the cancer. ^{1 2 3 4 9}

Research Team

Alexander Shoushtari

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Iovance Biotherapeutics, Inc.

Industry Sponsor

Trials

26

Recruited

1,800+

Findings from Research

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]

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 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]

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 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]

References

1. United States 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. [2022]

2. England 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Clinical efficacy of T-cell therapy after short-term BRAF-inhibitor priming in patients with checkpoint inhibitor-resistant metastatic melanoma. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy with tumor-infiltrating lymphocytes and subcutaneous recombinant interleukin-2 plus interferon alfa-2a for melanoma patients with nonresectable distant disease: a phase I/II pilot trial. Melanoma Istituto Scientifico Tumori Group. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical feasibility and treatment outcomes with nonselected autologous tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Rare immune-related adverse events in a patient with metastatic melanoma: a case report highlighting sarcoidosis-like reactions triggered by immune-checkpoint inhibitors. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Pilot study of local autologous tumor infiltrating lymphocytes for the treatment of recurrent malignant gliomas. [2020]

9. Greece pubmed.ncbi.nlm.nih.gov

Analysis of the proliferative and phenotypic properties of tumor infiltrating lymphocytes expanded in vitro in the course of the clinical trial of adoptive immunotherapy of metastatic melanoma. [2019]