Lifileucel for Uveal Melanoma
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Must not be taking: Immunosuppressants, Aminoglycosides
Disqualifiers: Organ allograft, Brain metastases, others
No Placebo Group
Approved in 1 Jurisdiction
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.12345
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.678910
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.
I am 18 years old or older.
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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.
See 9 more
Trial 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) (CAR T-cell Therapy)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Group I: Participants with Metastatic Uveal MelanomaExperimental Treatment1 Intervention
Participants have metastatic uveal melanoma who will undergo surgical excision to generate LN-144/LN-145
Group II: Participants with Metastatic SarcomaExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering WestchesterWest Harrison, NY
Memorial Sloan Kettering WestchesterHarrison, NY
Memorial Sloan Kettering Cancer Center (All Protocol Activities)New York, NY
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
Iovance Biotherapeutics, Inc.Industry Sponsor
References
Review of bi-specific therapies in uveal melanoma. [2023]Uveal melanoma is a rare subtype of melanoma that once metastatic portends a poor prognosis. Likely due to the distinct differences in biology, metastatic potential, and immunologic profile as compared to cutaneous melanoma, uveal melanoma's response to immune checkpoint inhibition has been disappointing. Bi-specific fusion protein therapies (T cell engagers) are a novel strategy to forcibly bridge the immune system with a target on a cancer cell. This approach has been explored in a number of cancer types and has recently demonstrated success in uveal melanoma. Tebentafusp, a first in class ImmTAC (Immune-mobilizing monoclonal TCRs against cancer), has now shown an overall survival benefit when compared to investigator's choice. This review aims to summarize the experience with this first in class bi-specific T cell engager as well as highlight bi-specifics as a novel treatment strategy in uveal melanoma.
First Drug Approved for Rare Eye Cancer. [2022]Tebentafusp, the first drug shown to extend overall survival in people with uveal melanoma, was greenlighted by the FDA in late January to treat patients with inoperable or metastatic forms of the aggressive eye cancer. The drug is also the first T-cell receptor therapy to reach the market.
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]We have shown that administration of a novel anti-CD54 monoclonal antibody (UV3) results in long-term survival of SCID mice bearing human myeloma xenografts. Previous studies have demonstrated a link between the expression of CD54 and the progression of uveal melanoma. Our study assessed the expression of CD54 on 7 human uveal melanoma cell lines and 3 cell lines established from uveal melanoma metastases. In vivo studies examined the efficacy of systemic and local administration of UV3 antibody on the progression of uveal melanoma cells transplanted either heterotopically or orthotopically into SCID mice. Five of the 7 primary uveal melanoma cell lines and all 3 of the metastases cell lines expressed CD54. Intraperitoneal injection of either IgG or F(ab')2 fragments of UV3 significantly inhibited the growth of subcutaneous and intraocular melanomas. Subconjunctival injection of either IgG or F(ab')2 fragments of UV3 produced a significant reduction in the growth of intraocular melanomas, even if the antibody was administered after the appearance of intraocular tumors. The results indicate that both primary and metastatic human uveal melanoma cells express CD54. The marked inhibition of intraocular and subcutaneous uveal melanoma progression suggests that UV3 antibody is a promising therapeutic agent for further evaluation in patients with uveal melanoma. This is especially noteworthy, as no existing therapeutic modality prevents metastasis of uveal melanoma or prolongs the survival of patients with uveal melanoma.
Treatment of primary intraocular melanoma. [2007]The treatment of intraocular melanoma has evolved recently. Enucleation has been superseded largely by brachytherapy, proton beam radiotherapy, stereotactic irradiation, trans-scleral local resection, transretinal resection and diode laser phototherapy. Many patients develop metastatic disease, which usually involves the liver and occurs hematogenously. Disseminated disease rarely responds to therapy, and is usually fatal within 1 year of the onset of symptoms. Uveal melanomas develop characteristic chromosomal abnormalities, such as loss of chromosome 3. This is associated with a reduction in the 5-year survival from approximately 95% to less than 50%.
Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma. [2023]Tebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive for HLA-A*02:01 and have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported a long-term survival benefit associated with the drug.
Effect of Aflibercept on Cystoid Macular Edema Associated with Central Retinal Vein Occlusion. Results from a District Hospital in the United Kingdom. [2022]The purpose of this study was to report the efficiency and safety of intravitreal aflibercept for the treatment of cystoid macular edema (CME) secondary to central retinal vein occlusion (CRVO).
Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER. [2021]An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD).
[Potential pitfalls of anti-VEGF therapy of neovascular age-related macular degeneration]. [2021]When administering anti-VEGF therapy for neovascular age-related macular degeneration (nAMD), it is necessary to take into account the fact that treatment outcomes - in addition to factors associated with the disease itself - may be affected by progressive concomitant conditions (for example, macular atrophy) and possible adverse events (AEs). The latter can be divided into two large groups: non-inflammatory and inflammatory. Intraocular inflammation (IOI) is a rare but potentially dangerous AE of anti-VEGF therapy, which can include endophthalmitis, early sterile inflammation and retinal vasculitis. Raising awareness about inflammatory AEs is becoming even more important due to the sheer number of intravitreal injections performed, as well as the frequency of cases of IOI when using new anti-VEGF drugs. The new anti-VEGF drug Brolucizumab is associated with the development of retinal vasculitis, which is considered a type III and IV hypersensitivity reaction (involving cellular and humoral immune responses, respectively). The article presents an overview of publications on the mechanisms, clinical manifestations, differentiation, and methods of treatment of various types of IOI.
The safety of ustekinumab for the treatment of psoriatic arthritis. [2017]The cytokines interleukin (IL)-12 and IL-23 have been involved in the pathogenesis of psoriasis and psoriatic arthritis. Ustekinumab is a fully human monoclonal antibody targeting the p40 subunit shared by IL-12 and IL-23. Ustekinumab prevents the interaction of IL-12 and IL-23 binding to their receptors, blocking the T1 and T17 inflammatory pathways. Ustekinumab has been evaluated for the treatment of various chronic immune mediated diseases including psoriasis and psoriatic arthritis (PsA). Most of the data regarding the safety of ustekinumab come from the experience treating patients with psoriasis, but clinical trials have demonstrated its efficacy and safety in the treatment of both diseases. The most common adverse events observed during the clinical trials are mild in intensity, and include respiratory tract infections, nasopharyngitis, headache and injection site reactions. Throughout long-term ustekinumab treatment, serious infections or major cardiovascular adverse events occurred rarely. Areas covered: In this review we report the safety data that come from phase II and phase III clinical trials that assay the efficacy and safety of ustekinumab in PsA, including recently published data corresponding to long-term studies. Relevant references were obtained through a literature search in MEDLINE/Pubmed (search strategy: ustekinumab AND psoriatic arthritis) for articles published until November 2016, complemented by a manual search. Expert opinion: In clinical practice, ustekinumab is generally a well-tolerated treatment, and the safety profile in psoriatic arthritis is similar to that reported in plaque psoriasis.
Fluocinolone acetonide intravitreal implant as a therapeutic option for severe Sjögren's syndrome-related keratopathy: a case report. [2020]In this report, we present the results of a severe case of Sjögren's syndrome-related keratopathy after fluocinolone acetonide 190-μg intravitreal implant (Iluvien®; Alimera Sciences Inc.) therapy.
Tebentafusp in the Treatment of Metastatic Uveal Melanoma: Patient Selection and Special Considerations. [2023]Uveal melanoma (UM) is a rare type of melanoma with distinct features from cutaneous melanoma, low response rates to immune checkpoint inhibition, and poor survival rates. Tebentafusp, a bispecific antibody engaging T cells with gp 100 on HLA-A*02:01, was recently approved by the FDA as the first drug of its class and the first treatment approved by the FDA to treat UM. In this review, we summarize the preclinical and clinical data on tebentafusp for UM. We additionally discuss patient selection and the relevant challenges. For the literature search, PubMed search and relevant articles presented at international conferences were used.
Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. [2022]Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells.
Prognostic significance of PD-1/PD-L1 expression in uveal melanoma: correlation with tumor-infiltrating lymphocytes and clinicopathological parameters. [2021]To understand how to improve the effect of immune checkpoint inhibitors in uveal melanoma (UM), we need a better understanding of the expression of PD-1 and PD-L1, their relation with the presence of tumor-infiltrating lymphocytes (TILs), and their prognostic relevance in UM patients.