Lifileucel for Uveal Melanoma

Recruiting at 3 trial locations

Overseen By Adam Schoenfeld, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Aminoglycosides

Disqualifiers: Organ allograft, 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: Variable

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called lifileucel, a type of cell therapy, for individuals with metastatic uveal melanoma, a type of eye cancer that has spread. The trial aims to evaluate the effectiveness and safety of lifileucel for these patients. Participants must have a confirmed diagnosis of metastatic uveal melanoma and at least one tumor suitable for creating the treatment. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

The trial requires a washout period for certain medications before starting treatment. If you're on targeted therapy, you need a washout of at least 14 days or 5 half-lives, whichever is longer. For chemotherapy and immunotherapy, a 21-day washout is required. The protocol does not specify other medications, so consult with the trial team for guidance on your specific medications.

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

Research has shown that lifileucel, also known as LN-144, may help treat certain cancers, such as melanoma. In earlier studies, patients who received lifileucel experienced significant benefits, even after undergoing multiple treatments. This suggests the treatment can be effective and generally well-tolerated.

The treatment uses a person's own immune cells, which are grown and then reintroduced into the body to help fight cancer. This approach, called tumor-infiltrating lymphocyte (TIL) therapy, has received FDA approval for some skin cancers, indicating it is considered safe.

While specific side effects are not listed here, the FDA's approval for other cancers suggests that any side effects are manageable and acceptable compared to the benefits. However, discussing potential risks with a doctor is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Lifileucel (LN-144) is unique because it leverages tumor-infiltrating lymphocytes (TILs) to fight metastatic uveal melanoma. Unlike traditional treatments like chemotherapy or targeted therapies, which may not effectively tackle this rare type of melanoma, Lifileucel harnesses the body's own immune cells to target and destroy cancer cells. This personalized approach not only offers a new mechanism of action but also holds promise for improved efficacy by boosting the immune response directly against the tumor. Researchers are excited because this innovative method could offer a more effective and targeted treatment option for patients with limited choices.

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

Research has shown that lifileucel, a type of cell therapy, holds promise for treating melanoma. Lifileucel uses the body's own immune cells, known as tumor-infiltrating lymphocytes (TILs), to combat cancer cells. Previous studies found lifileucel effective for patients who have already tried other treatments. Its approval for some types of melanoma highlights its potential effectiveness. This trial tests lifileucel for treating metastatic uveal melanoma, a challenging form of eye cancer. ^{1 2 5 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 over 18 with metastatic uveal melanoma, who have at least one lesion suitable for TIL harvesting. Participants must not be pregnant or breastfeeding, free from certain infections and systemic illnesses, not on immunosuppressive therapy (except steroids for adrenal insufficiency), and without a history of organ transplant or cell transfer therapy.

Inclusion Criteria

I understand the study's requirements and have given my written consent.

My blood counts and organ functions are within normal ranges.

You should not have specific infections like HIV, Hepatitis B and C, Syphilis, CMV, EBV, HSV, or COVID-19.

Exclusion Criteria

You have a condition where your immune system does not work properly from birth.

I have a heart, lung, or other specific health condition.

I have had an organ transplant or cell therapy with strong chemotherapy.

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/LN-145

1-2 weeks

Treatment

Participants receive lifileucel (LN-144) for metastatic uveal melanoma

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Lifileucel (LN-144)

Trial Overview The study is testing lifileucel (LN-144) in patients with metastatic uveal melanoma. It's an open-label pilot trial, meaning both the researchers and participants know what treatment is being given. The focus is on evaluating the safety and effectiveness of LN-144 derived from the patient's own tumor cells.

How Is the Trial Designed?

Group I: Participants with Metastatic Uveal Melanoma Experimental Treatment 1 Intervention

Participants have metastatic uveal melanoma who will undergo surgical excision to generate LN-144/LN-145

Group II: Participants with Metastatic Sarcoma Experimental Treatment 1 Intervention

Participants have metastatic sarcoma who will undergo surgical excision to generate LN-144/LN-145

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+

Published Research Related to This Trial

In a study of 71 uveal melanoma tissue samples, PD-1 was expressed in 30 cases and PD-L1 in 44 cases, indicating a significant presence of these immune checkpoint proteins that could affect treatment outcomes.

The presence of tumor-infiltrating lymphocytes (TILs) was associated with higher PD-1 and PD-L1 expression, suggesting that TILs may promote aggressive tumor behavior and hinder the effectiveness of immune checkpoint inhibitors in uveal melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic significance of PD-1/PD-L1 expression in uveal melanoma: correlation with tumor-infiltrating lymphocytes and clinicopathological parameters. Singh, L., Singh, MK., Kenney, MC., et al.[2021]

Tebentafusp is the first drug approved by the FDA that has been shown to extend overall survival in patients with inoperable or metastatic uveal melanoma, a type of aggressive eye cancer.

It is also notable for being the first T-cell receptor therapy to be made available on the market, representing a significant advancement in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Drug Approved for Rare Eye Cancer. [2022]

Uveal melanoma, a rare and aggressive form of melanoma, has shown poor responses to traditional immune checkpoint inhibitors, highlighting the need for new treatment strategies.

Tebentafusp, a first-in-class bi-specific fusion protein therapy, has demonstrated a significant overall survival benefit in patients with uveal melanoma compared to standard treatment options, marking a promising advancement in this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of bi-specific therapies in uveal melanoma. Orloff, M., Seedor, R., Sato, T.[2023]

The novel anti-CD54 monoclonal antibody (UV3) significantly inhibited the growth of both primary and metastatic uveal melanoma in SCID mice, indicating its potential as an effective treatment option.

UV3 demonstrated long-term survival benefits in mice with human myeloma xenografts, suggesting it could be a promising therapeutic agent for patients with uveal melanoma, especially since current treatments do not effectively prevent metastasis or improve survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of an anti-CD54 (ICAM-1) monoclonal antibody (UV3) on the growth of human uveal melanoma cells transplanted heterotopically and orthotopically in SCID mice. Wang, S., Coleman, EJ., Pop, LM., et al.[2016]

Recent advancements in the treatment of intraocular melanoma have shifted from enucleation to more targeted therapies like brachytherapy and proton beam radiotherapy, improving treatment options for patients.

Patients with uveal melanoma who exhibit loss of chromosome 3 face a significantly reduced 5-year survival rate, dropping from about 95% to less than 50%, highlighting the importance of genetic factors in prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of primary intraocular melanoma. Damato, B.[2007]

Intravitreal aflibercept significantly improved visual acuity and reduced central retinal thickness in patients with cystoid macular edema secondary to central retinal vein occlusion, with a median follow-up of 6 months and a median of 4 injections.

The treatment was found to be safe, as no adverse effects or complications were reported during the study involving 10 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Aflibercept on Cystoid Macular Edema Associated with Central Retinal Vein Occlusion. Results from a District Hospital in the United Kingdom. Panos, GD., Kostakis, VT., Porter, GM.[2022]

Anti-VEGF therapy for neovascular age-related macular degeneration (nAMD) can lead to serious adverse events, particularly intraocular inflammation (IOI), which includes conditions like endophthalmitis and retinal vasculitis.

The new anti-VEGF drug Brolucizumab has been linked to retinal vasculitis, highlighting the importance of monitoring for inflammatory reactions as it involves complex immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Potential pitfalls of anti-VEGF therapy of neovascular age-related macular degeneration]. Kovalevskaya, MA., Pererva, OA., Roldugin, AA., et al.[2021]

In a review of 1817 patients from the HAWK and HARRIER trials, brolucizumab was associated with a 4.6% incidence of intraocular inflammation (IOI), which included cases of retinal vasculitis and vascular occlusion, indicating a notable risk of these complications compared to aflibercept, which had a 1.1% incidence of IOI.

Among the brolucizumab-treated patients, there were 8 cases of significant visual acuity loss (≥15 ETDRS letters), with most of these events occurring within 3 to 6 months after the first injection, highlighting the importance of monitoring for visual changes shortly after treatment initiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER. Monés, J., Srivastava, SK., Jaffe, GJ., et al.[2021]

Ustekinumab is an effective treatment for psoriasis and psoriatic arthritis, targeting the IL-12 and IL-23 cytokines to block inflammatory pathways, with clinical trials showing its efficacy and safety.

The treatment is generally well-tolerated, with most adverse events being mild, such as respiratory infections and headaches, and serious complications like major infections or cardiovascular events occurring rarely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of ustekinumab for the treatment of psoriatic arthritis. López-Ferrer, A., Laiz, A., Puig, L.[2017]

A 52-year-old woman with severe Sjögren's syndrome-related keratopathy showed significant improvement in her left eye after receiving an off-label intravitreal fluocinolone acetonide implant, with no further surgical interventions needed over a 6-month follow-up period.

In contrast, her right eye continued to experience complications requiring multiple surgeries, suggesting that fluocinolone acetonide may be an effective treatment option for severe autoimmune corneal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluocinolone acetonide intravitreal implant as a therapeutic option for severe Sjögren's syndrome-related keratopathy: a case report. Wasielica-Poslednik, J., Pfeiffer, N., Gericke, A.[2020]

Tebentafusp is the first FDA-approved treatment specifically for uveal melanoma (UM), a rare form of melanoma that typically has low response rates to existing therapies.

This bispecific antibody works by engaging T cells with gp 100 on HLA-A*02:01, highlighting a novel mechanism of action that targets UM more effectively than traditional immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tebentafusp in the Treatment of Metastatic Uveal Melanoma: Patient Selection and Special Considerations. Montazeri, K., Pattanayak, V., Sullivan, RJ.[2023]

In a phase 3 trial involving 378 patients with metastatic uveal melanoma, treatment with tebentafusp led to a significant increase in overall survival at 1 year (73%) compared to the control group (59%), demonstrating its efficacy as a new treatment option.

Tebentafusp was associated with manageable treatment-related adverse events, primarily cytokine-mediated and skin-related, which decreased in severity after initial doses, indicating a favorable safety profile with no treatment-related deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. Nathan, P., Hassel, JC., Rutkowski, P., et al.[2022]

In a phase 3 trial involving HLA-A*02:01-positive patients with untreated metastatic uveal melanoma, tebentafusp demonstrated a median overall survival of 21.6 months compared to 16.9 months in the control group, indicating a significant survival benefit.

The treatment was generally well-tolerated, with common side effects including rash and fever, but no new adverse events were reported with long-term use, and no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma. Hassel, JC., Piperno-Neumann, S., Rutkowski, P., et al.[2023]

Citations

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

NCT02360579 | Study of Lifileucel (LN-144), Autologous ... Lifileucel is an autologous adoptive cell transfer therapy that utilizes a TIL manufacturing process, as originally developed by the NCI, for the treatment ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9748991/

Efficacy and safety of lifileucel, a one-time autologous tumor ... In summary, one-time treatment with lifileucel TIL cell therapy demonstrated clinically meaningful activity in heavily pretreated patients with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06940739

A Study to Investigate the Safety and Efficacy of IOV-3001 ... A Study to Investigate the Safety and Efficacy of IOV-3001 in Adults With Advanced Melanoma Who Will Receive Lifileucel. ClinicalTrials.gov ID NCT06940739.

4. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/fda-amtagvi-til-therapy-melanoma

Lifileucel First Cellular Therapy Approved for Cancer - NCI FDA has approved lifileucel (Amtagvi), the first cancer treatment that uses immune cells called tumor-infiltrating lymphocytes, or TILs.

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

Tumor-Infiltrating Lymphocyte Cell Therapy for the ... The approval of lifileucel was based on an analysis of 73 patients in this study who received lifileucel at the recommended dos- ing range of 7.5 × 109 to 72 × ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/31/19/4004/765498/FDA-Approval-Summary-Lifileucel-for-Unresectable

Lifileucel for Unresectable or Metastatic Melanoma Previously ... The dual primary endpoints of this trial are ORR and progression-free survival, with overall survival as a key secondary endpoint. Iovance Biotherapeutics ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0147027225000790

Current perspectives on Lifileucel tumor-infiltrating ... Furthermore, while Lifileucel TIL immunotherapy has shown encouraging outcomes in melanoma treatment, its efficacy in other cancer types has yet to be ...