Lifileucel for Uveal Melanoma

Recruiting at 2 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

Trial Summary

What is the purpose of this trial?

This trial is testing lifileucel, a treatment that uses a patient's own immune cells, in patients with advanced uveal melanoma. The treatment aims to boost the body's natural ability to fight cancer. Lifileucel has shown promising results in treating melanoma that does not respond to other treatments.

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.

What data supports the idea that Lifileucel for Uveal Melanoma is an effective treatment?

The available research does not provide specific data on Lifileucel for Uveal Melanoma. Instead, it highlights Tebentafusp as a drug that has shown success in treating uveal melanoma by extending overall survival in patients. This suggests that while Lifileucel might be a promising treatment, the current evidence does not directly support its effectiveness for uveal melanoma compared to Tebentafusp, which has demonstrated clear benefits. ^{1 2 3 4 5}

What safety data is available for Lifileucel in treating uveal melanoma?

The provided research does not contain any safety data for Lifileucel or its related names in the treatment of uveal melanoma. The studies focus on other treatments and conditions, such as aflibercept for macular edema, brolucizumab for macular degeneration, ustekinumab for psoriatic arthritis, and fluocinolone acetonide for keratopathy. ^{6 7 8 9 10}

Is Lifileucel a promising treatment for uveal melanoma?

The information provided does not mention Lifileucel as a promising treatment for uveal melanoma. Instead, it highlights Tebentafusp as a new and effective drug for this type of cancer, showing improved survival rates for patients. ^{1 2 11 12 13}

Research Team

Alexander Shoushtari

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Review of bi-specific therapies in uveal melanoma. [2023]

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

First Drug Approved for Rare Eye Cancer. [2022]

3. United States 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. [2016]

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

Treatment of primary intraocular melanoma. [2007]

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

Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma. [2023]

6. Germany 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. [2022]

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

Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER. [2021]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Potential pitfalls of anti-VEGF therapy of neovascular age-related macular degeneration]. [2021]

9. England pubmed.ncbi.nlm.nih.gov

The safety of ustekinumab for the treatment of psoriatic arthritis. [2017]

10. England pubmed.ncbi.nlm.nih.gov

Fluocinolone acetonide intravitreal implant as a therapeutic option for severe Sjögren's syndrome-related keratopathy: a case report. [2020]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Tebentafusp in the Treatment of Metastatic Uveal Melanoma: Patient Selection and Special Considerations. [2023]

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

Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

Prognostic significance of PD-1/PD-L1 expression in uveal melanoma: correlation with tumor-infiltrating lymphocytes and clinicopathological parameters. [2021]