Tumor Infiltrating Lymphocytes for Uveal Melanoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Udai Kammula
Must not be taking: Systemic steroids, Anti-infectives
Disqualifiers: Pregnancy, Immunodeficiency, Autoimmune, others
No Placebo Group
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?This is a Phase 2 study in which the efficacy of a non-myeloablative lymphodepleting preparative regimen followed by infusion of autologous TIL and high-dose aldesleukin in patients with metastatic uveal melanoma will be evaluated.
Metastatic uveal melanoma (UM) carries a poor prognosis with estimated survival of 4-6 months. There are no known effective systemic therapies. Metastatic UM is classified as an "orphan" disease and there are currently few clinical trial options for these patients. Thus, novel systemic approaches are desperately needed.
A recent pilot study has found that administration of autologous tumor infiltrating lymphocytes (TIL) generated from resected metastases can induce objective tumor response and durable complete response in metastatic uveal melanoma patients. These encouraging results require confirmation to determine if this immunotherapy is of future benefit in treating this disease.
Will I have to stop taking my current medications?
The trial requires that more than four weeks have passed since any prior systemic therapy before starting the preparative regimen, and any side effects from previous treatments must have improved to a manageable level. This suggests you may need to stop certain medications before participating.
What data supports the effectiveness of the treatment Tumor Infiltrating Lymphocytes (TIL), Lifileucel, Amtagvi for uveal melanoma?
Lifileucel, a treatment using tumor-infiltrating lymphocytes, has shown effectiveness in treating advanced melanoma, with a 36% response rate in patients who had limited options after other treatments. This suggests potential for similar effectiveness in uveal melanoma, as TILs can be expanded from primary uveal melanoma for treatment.
12345Is Tumor Infiltrating Lymphocytes (TIL) therapy safe for humans?
TIL therapy, including lifileucel, has been studied in patients with advanced melanoma and has shown a safety profile consistent with the use of lymphodepleting chemotherapy and high-dose interleukin-2, with no treatment-related deaths reported.
12356How is the treatment Tumor Infiltrating Lymphocytes (TIL) unique for uveal melanoma?
Tumor Infiltrating Lymphocytes (TIL) therapy is unique for uveal melanoma because it involves using the patient's own immune cells, which are extracted from the tumor, expanded in the lab, and then reintroduced to help fight the cancer. This approach is different from standard treatments as it leverages the body's immune system to target cancer cells more specifically.
12789Eligibility Criteria
This trial is for adults aged 18-75 with measurable metastatic uveal melanoma, normal organ function tests, and specific blood count levels. They must not have HIV or hepatitis B/C, be willing to use birth control, and can't be pregnant or breastfeeding. Those with certain heart conditions, severe allergies to study drugs, autoimmune diseases, active infections or on steroids are excluded.Inclusion Criteria
I had surgery to remove cancer that spread to my brain.
I am fully active or can carry out light work.
It's been over 4 weeks since my last systemic therapy, and any side effects are under control.
+17 more
Exclusion Criteria
Your heart's pumping ability is less than 45%.
I have a serious autoimmune disease affecting major organs.
I am currently on systemic steroid therapy.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Cell Preparation
Resection of tumor to obtain TIL, which are then grown and expanded for the trial
Variable, based on cell growth
Treatment
Lymphocyte depleting preparative regimen followed by infusion of TIL and high-dose aldesleukin
6 weeks (+/- 2 weeks)
Multiple visits for chemotherapy and TIL infusion
Follow-up
Participants are monitored for safety, tumor response, and immunologic parameters
Up to 24 months
Measurements taken at 6 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months, 24 months
Participant Groups
The trial studies the effectiveness of Tumor Infiltrating Lymphocytes (TIL) therapy combined with high-dose aldesleukin in patients with metastatic uveal melanoma after a non-myeloablative lymphodepleting regimen. It aims to confirm promising results from a pilot study indicating potential tumor response.
1Treatment groups
Experimental Treatment
Group I: Tumor Infiltrating Lymphocytes (TIL)Experimental Treatment1 Intervention
Patients with uveal melanoma will receive the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide followed by infusion of up to 2x10\^11 TIL infused intravenously through a central vein catheter and Aldesleukin, administered at a dose of 600,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period approximately every 8 hours beginning within 24 hours of TIL infusion and continuing for up to a maximum of 6 doses.
Tumor Infiltrating Lymphocytes (TIL) is already approved in United States for the following indications:
🇺🇸 Approved in United States as Lifileucel (Amtagvi) for:
- Advanced melanoma that has worsened after treatment with certain immunotherapy drugs or targeted therapies
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UPMC Hillman Cancer CenterPittsburgh, PA
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Who Is Running the Clinical Trial?
Udai KammulaLead Sponsor
References
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.
Tumor-Infiltrating T Cells Can Be Expanded Successfully from Primary Uveal Melanoma after Separation from Their Tumor Environment. [2022]To evaluate whether expanded tumor-infiltrating lymphocytes (TILs) can be obtained from primary uveal melanoma (UM) for potential use as adjuvant treatment in patients at risk of developing metastatic disease.
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]Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma.
Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma. [2022]Effective treatment options are limited for patients with advanced (metastatic or unresectable) melanoma who progress after immune checkpoint inhibitors and targeted therapies. Adoptive cell therapy using tumor-infiltrating lymphocytes has demonstrated efficacy in advanced melanoma. Lifileucel is an autologous, centrally manufactured tumor-infiltrating lymphocyte product.
Ocular and systemic autoimmunity after successful tumor-infiltrating lymphocyte immunotherapy for recurrent, metastatic melanoma. [2021]To describe the ophthalmic and systemic autoimmune findings after successful adoptive cell transfer of ex vivo expanded, autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) for metastatic melanoma.
Clinical feasibility and treatment outcomes with nonselected autologous tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma. [2022]Nonselected autologous tumor-infiltrating lymphocytes (TILs) may provide advantages over other treatments for solid tumors, including checkpoint inhibitor-refractory melanoma. This retrospective analysis reports a single-center experience of nonselected autologous TILs derived from digested tumors for compassionate use treatment of advanced cutaneous melanoma, including after programmed cell death protein 1 (PD-1) inhibition. Patients with histologically confirmed metastatic cutaneous melanoma and no standard-of-care treatment options underwent tumor resection for TIL product manufacturing. Patients received lymphodepleting chemotherapy with cyclophosphamide for 2 days and fludarabine for 5 days, followed by a single TIL infusion and post-TIL high-dose interleukin (IL)-2. Safety assessments included clinically significant adverse events (AEs). Efficacy assessments included overall response rate (ORR), complete response (CR) rate, disease control rate (DCR), and overall survival. Between October 2011 and August 2019, 21 patients underwent treatment (median follow-up time, 52.2 months from TIL infusion). Among all treated patients, median age was 45 years, median number of disease sites was 4, 100% had M1c or M1d disease, and 90% received prior checkpoint inhibitor. Twelve patients received TILs after prior PD-1 inhibition. The safety profile among all treated patients and the prior PD-1 inhibitor subgroup was generally consistent with lymphodepletion and high-dose IL-2. No treatment-related deaths occurred. Among all patients, the ORR was 67%, CR rate was 19%, and the DCR was 86%, which was consistent with that observed in the prior PD-1 inhibitor subgroup (58%, 8%, and 75%, respectively). Median overall survival in all treated patients and the prior PD-1 inhibitor subgroup was 21.3 months. In total, 5 patients (24%) had durable ongoing responses (>30 months post-TIL infusion) at data cutoff, and all patients who achieved CR remained alive and disease free. To further illustrate how TIL therapy may integrate into established treatment paradigms, several case studies of patients treated in this series were included. Overall, these data demonstrate that manufacturing of nonselected autologous TILs from tumor digests is feasible and resulted in high rates of durable response in poor-risk patient populations, which may address significant unmet medical need.
Immunohistochemistry of infiltrating lymphocytes in uveal malignant melanoma. [2010]To investigate using immunohistochemistry the unusual finding that tumor infiltrating lymphocytes (TIL) in uveal melanomas are associated with a higher mortality rate.
Uveal melanomas contain antigenically specific and non-specific infiltrating lymphocytes. [2019]Tumor-infiltrating lymphocytes (TIL) were recovered from a series of human choroidal melanomas and expanded in cultures containing interleukin-2 (IL-2) to determine whether TIL contained cytotoxic cells that could be activated in vitro.
Analysis of lymphocytic infiltration in uveal melanoma. [2015]Among 27 uveal melanomas, five were found to contain tumor infiltrating lymphocytes (TILs). Four had high levels of lymphocytes, and the fifth had comparatively low levels but adequate numbers for comprehensive analysis. The TILs were analyzed by flow cytometry to determine the relative proportions of lymphocyte subsets and markers of lymphocyte activation. The results show the predominance of T-suppressor/cytotoxic lymphocytes and insignificant levels of B-cells present in the infiltrate. The T-suppressor/cytotoxic cells were generally activated to a higher degree than the T-helper cells when assayed for levels of the histocompatibility antigen, HLA-DR. T-helper cells expressed more interleukin (IL-2) receptor (Tac) than T-suppressor/cytotoxic cells.