Actively Recruiting
Assessment of the Safety and Tolerability of ex Vivo Next-generation Neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) Therapy in Advanced Epithelial Tumors and Immune Checkpoint Blockade (ICB) Resistant Solid Tumors
Led by Vall d'Hebron Institute of Oncology · Updated on 2024-11-07
10
Participants Needed
1
Research Sites
270 weeks
Total Duration
On this page
Sponsors
V
Vall d'Hebron Institute of Oncology
Lead Sponsor
B
Banc de Sang i Teixits
Collaborating Sponsor
AI-Summary
What this Trial Is About
Background: The presence of T-lymphocytes in resected tumor samples derived from long-term survival patients and the fact that reinvigoration of their functionality through the administration of specific immune-therapies can lead to remarkable antitumor responses supports that lymphocytes play a critical role in cancer immunity. Adoptive cell therapy using tumor-infiltrating lymphocytes product (TIL-ACT) is a well-established combination therapy currently under study in several world reference centers, using an autologous cell product without genetic modifications. This cell product consists of tumor-infiltrating lymphocytes (TIL), which are collected from the patient and expanded in the lab under specific conditions to enhance its antitumoral efficacy before reinfusion in the same patient. However, this cell product alone does not achieve adequate efficacy, and a combination of both previous non-myeloablative lymphodepleting (NMA-LD) chemotherapy and subsequent cytokine therapy (specifically IL-2) is needed to support the expansion of the infused cells. The investigators hypothesize that TILs enriched for neoantigen recognition are superior to unselected TILs at mediating tumor regression in patients with epithelial tumors and even other solid tumors where immune checkpoint blockade (ICB) is approved and used as part of standard therapy. The investigators propose to manufacture a T-cell product composed of TILs that are selected based on their ability to recognize patient-specific neoantigens and to use these to treat patients with metastatic, refractory, epithelial cancers, as well as ICB-resistant solid tumors. Furthermore, it also proposed to study the tumor and T cells at baseline and after treatment to investigate whether specific phenotypic and functional traits may be associated with clinical outcome. Primary objective: To evaluate the safety and the tolerability of ex vivo next generation neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) in patients with metastatic or unresectable epithelial tumors and immune checkpoint blockade (ICB) resistant solid tumors. Secondary objectives: * To determine the success in producing active specific TILs from our target patients. * To evaluate the initial clinical activity of the NEXTGEN-TIL products in our target patients.
CONDITIONS
Official Title
Assessment of the Safety and Tolerability of ex Vivo Next-generation Neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) Therapy in Advanced Epithelial Tumors and Immune Checkpoint Blockade (ICB) Resistant Solid Tumors
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Have histologically or cytologically confirmed metastatic or unresectable solid tumors that have progressed after at least one standard therapy or no standard therapy is available
- Have at least one tumor lesion suitable for biopsy or resection to obtain tumor-infiltrating lymphocytes
- Be 18 years old or older
- Understand and voluntarily sign informed consent
- Be able and willing to follow the study schedule and requirements
- Have an ECOG performance status of 0 or 1
- Be medically fit to undergo all study procedures
- Have documented left ventricular ejection fraction of 45% or higher
- Have pulmonary function test results (FEV1, FVC, DLCO) of 50% or higher
- Be seronegative for HIV antibody
- Be seronegative for active hepatitis B and hepatitis C, with specific criteria for past infection
- Have a life expectancy of at least 6 months
- Agree to use effective contraception during the study and for 6 months after last IL-2 dose if of childbearing potential or have a partner of childbearing potential
- After tumor biopsy, have remaining measurable disease by RECIST criteria
- Meet specific hematological, renal, and hepatic function thresholds
- Have recovered from prior treatment toxicities to grade 1 or less, except certain allowed conditions
- Have recovered from minor surgeries within the past 3 weeks
You will not qualify if you...
- Have symptomatic or untreated brain metastases or leptomeningeal carcinomatosis
- Have had an invasive malignancy within the past 3 years except certain low-risk cancers
- Have active systemic infection requiring treatment within 14 days before lymphodepleting therapy
- Have active hepatitis B or C infection
- Have active autoimmune disease requiring immunosuppressive treatment
- Have history of organ or bone marrow transplantation
- Have primary immunodeficiency such as AIDS
- Require regular steroids above prednisone 10 mg/day (some exceptions apply)
- Have uncontrolled or progressive significant organ diseases within the last 6 months
- Have history of coronary revascularization or ischemic symptoms
- Have idiopathic pulmonary fibrosis or active pneumonitis
- Are allergic to any treatment compounds
- Have contraindications to cyclophosphamide, fludarabine, or IL-2
- Have received anticancer therapies or investigational agents within specified recent timeframes
- Have had major surgery within 3 weeks before lymphodepleting therapy
- Have previously received investigational cell or gene therapies
- Are pregnant or breastfeeding
- Have conditions that may interfere with study compliance or follow-up
AI-Screening
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Trial Site Locations
Total: 1 location
1
Vall d'Hebron Institute of Oncology
Barcelona, Spain
Actively Recruiting
Research Team
E
Elena Garralda
CONTACT
S
Susana Muñoz
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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