At a glance
ClinicalIndex Comparison Record- ✓Metastatic or unresectable solid tumors with progression on standard therapy
- ✓At least one adequate lesion for resection or biopsy for TIL generation
- ✓Age ≥18 years
- ✓ECOG performance status 0 or 1
- ✕Symptomatic and/or untreated brain metastases
- ✕Leptomeningeal carcinomatosis
- ✕Active malignancy within past 3 years (except non-melanoma skin cancer, cervical/bladder CIS, DCIS, prostate cancer in remission)
- ✕Active systemic infection requiring anti-infective treatment within 14 days
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
A Phase I Study to Assess 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
In Brief
A Early Phase 1 clinical trial evaluating NEXTGEN-TIL, Non-myeloablative Lymphodepletion (NMA-LD) Regimen, and 1 other intervention for Epithelial Tumors, Malignant and Malignant Solid Tumor. Currently recruiting, targeting 10 participants across 1 site.
Detailed Summary
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.
Study Details
Timeline
Interventions
NEXTGEN-TIL product is a cellular investigational product comprising a live cell suspension of autologous tumor-infiltrating lymphocytes derived from the patient's own tumor. Each dose contains at least 5 x 10\^8 total viable lymphocytes, and a maximum of 1.11x10\^11. It will be administered IV on Day 0 (24h after the last dose of Fludarabine).
Patients will receive a NMA-LD chemotherapy based on Cyclophosphamide 60 mg/kg IV (once daily on Days -5 and -4) and Fludarabine 25 mg/m2 IV (once daily on Days -5 to -1).
Patients will receive sequential doses of 720,000 IU/kg IV IL-2 every 8-24 hours depending on patient tolerance. It will be administered on Days 0 to 2, starting between 3 and 24 hours after the completion of NEXTGEN-TIL infusion. IL-2 doses may be skipped in case of toxicity. If 2 sequential doses or more than 2 non-sequential doses of IL-2 are skipped due to patient intolerance or the discretion of the investigator, IL-2 administration must be stopped.