TIL + Nivolumab for Lung Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Must not be taking: PD-1 inhibitors
Disqualifiers: Autoimmune disease, Rapidly progressing tumors, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?To determine the effect of a special preparation of cells, called tumor-infiltrating lymphocytes (TIL) stimulated with CD40L, when given with the drug nivolumab, for patients with EGFR, ALK, ROS1, or HER2-genomically altered lung cancer.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should not be on chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment, except for certain exceptions like low-dose oral hydrocortisone for adrenal insufficiency.
What data supports the effectiveness of the treatment TIL + Nivolumab for lung cancer?
In a phase 1 trial, the combination of tumor-infiltrating lymphocyte (TIL) therapy and the drug nivolumab showed preliminary signs of effectiveness in patients with advanced non-small cell lung cancer, with some patients experiencing a reduction in tumor size and a few achieving complete responses lasting over a year.
12345Is the combination of TIL therapy and Nivolumab safe for humans?
The combination of tumor-infiltrating lymphocyte therapy and the drug Nivolumab has been considered safe and tolerable in a phase I clinical trial for patients with advanced lung cancer. However, immune-related side effects, such as skin issues, are common with Nivolumab and similar drugs.
46789How is the TIL + Nivolumab treatment different from other treatments for lung cancer?
The TIL + Nivolumab treatment is unique because it combines tumor-infiltrating lymphocytes (TILs), which are immune cells extracted and expanded from a patient's own tumor, with Nivolumab, an immune checkpoint inhibitor. This approach aims to enhance the body's immune response against cancer, especially in cases where patients have not responded to Nivolumab alone.
1251011Eligibility Criteria
This trial is for adults over 18 with stage IV or recurrent NSCLC who have specific genetic alterations (EGFR, ALK, ROS1, HER2) and have progressed after at least one systemic therapy. They must have a tumor that can be biopsied for TIL harvest and adequate organ function. Those with certain heart conditions, uncontrolled illnesses, more than six prior NSCLC therapies, previous PD-1/PD-L1 inhibitor treatment for metastatic NSCLC or active infections are excluded.Inclusion Criteria
I am fully active or can carry out light work.
My NSCLC worsened after treatment, including targeted therapy if applicable.
My brain metastases are stable or treated, and I don't need immediate brain-specific treatment.
+6 more
Exclusion Criteria
You have received an organ from someone else in the past.
You have had a serious allergic reaction to beta-lactam antibiotics in the past.
My cancer is growing quickly, according to my doctor.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive nivolumab infusion every 3 weeks prior to lymphodepletion chemotherapy with cyclophosphamide/fludarabine, followed by TIL infusion and interleukin-2, then nivolumab infusion every 4 weeks up to 12 months
12 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 5 years
Participant Groups
The trial tests the effectiveness of CD40L-stimulated TILs combined with nivolumab in patients with genetically altered lung cancer. It aims to see how well these specially prepared immune cells work when given alongside an established immunotherapy drug.
1Treatment groups
Experimental Treatment
Group I: TIL+ NivolumabExperimental Treatment6 Interventions
Nivolumab infusion every 3 weeks prior to lymphodepletion chemotherapy with cyclophosphamide/fludarabine, TIL infusion and interleukin-2. Then nivolumab infusion every 4 weeks up to 12 months.
Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:
🇺🇸 Approved in United States as Opdivo for:
- Advanced or metastatic gastric cancer
- Gastroesophageal junction cancer
- Esophageal adenocarcinoma
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Esophageal squamous cell carcinoma
🇪🇺 Approved in European Union as Opdivo for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Gastroesophageal junction cancer
- Esophageal adenocarcinoma
🇨🇦 Approved in Canada as Opdivo for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Gastroesophageal junction cancer
- Esophageal adenocarcinoma
🇨🇭 Approved in Switzerland as Opdivo for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Gastroesophageal junction cancer
- Esophageal adenocarcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
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Who Is Running the Clinical Trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
References
Massive PD-L1 and CD8 double positive TILs characterize an immunosuppressive microenvironment with high mutational burden in lung cancer. [2022]Programmed cell death ligand 1 (PD-L1) expressed on tumor and immune cells are both associated with the response to programmed cell death 1 (PD-1) pathway blockade therapy. Here, we examine the role of CD8+PD-L1+ tumor-infiltrating lymphocyte (Tils) in the tumor microenvironment of non-small cell lung cancer (NSCLC).
TCF1+PD-1+ tumour-infiltrating lymphocytes predict a favorable response and prolonged survival after immune checkpoint inhibitor therapy for non-small-cell lung cancer. [2022]Label="BACKGROUND">T-cell factor 1 (TCF1)+Programmed cell death-1 (PD-1)+ tumour-infiltrating lymphocytes (TILs) are a recently defined subset of exhausted T-cells (Texh-cells) that exhibit a progenitor phenotype. They have been associated with a response to immune checkpoint inhibitor (ICI) therapy in murine tumour models and in patients with malignant melanoma. We investigated the significance of TCF1+PD-1+ TILs as a predictive biomarker for ICI therapy response in non-small-cell lung cancer (NSCLC).
The prognostic value of tumor-infiltrating lymphocytes in non-small cell lung cancer patients who received neoadjuvant chemotherapy followed by surgery. [2023]The relationship between tumor-infiltrating lymphocyte (TIL) levels and the prognosis of patients with non-small cell lung cancer (NSCLC) who receive neoadjuvant chemotherapy followed by surgery is a problem that requires more research.
Tumor-Infiltrating Lymphocytes Help Rein In NSCLC. [2021]In a phase I clinical trial, tumor-infiltrating lymphocyte therapy combined with the anti-PD-1 drug nivolumab was considered safe and tolerable-and exhibited preliminary signs of efficacy-in patients with stage IV or recurrent non-small cell lung cancer.
Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial. [2023]Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown activity in melanoma, but has not been previously evaluated in metastatic non-small cell lung cancer. We conducted a single-arm open-label phase 1 trial ( NCT03215810 ) of TILs administered with nivolumab in 20 patients with advanced non-small cell lung cancer following initial progression on nivolumab monotherapy. The primary end point was safety and secondary end points included objective response rate, duration of response and T cell persistence. Autologous TILs were expanded ex vivo from minced tumors cultured with interleukin-2. Patients received cyclophosphamide and fludarabine lymphodepletion, TIL infusion and interleukin-2, followed by maintenance nivolumab. The end point of safety was met according to the prespecified criteria of ≤17% rate of severe toxicity (95% confidence interval, 3-29%). Of 13 evaluable patients, 3 had confirmed responses and 11 had reduction in tumor burden, with a median best change of 35%. Two patients achieved complete responses that were ongoing 1.5 years later. In exploratory analyses, we found T cells recognizing multiple types of cancer mutations were detected after TIL treatment and were enriched in responding patients. Neoantigen-reactive T cell clonotypes increased and persisted in peripheral blood after treatment. Cell therapy with autologous TILs is generally safe and clinically active and may constitute a new treatment strategy in metastatic lung cancer.
Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinib. [2023]Concurrent programmed death-ligand-1 (PD-(L)1) plus osimertinib is associated with severe immune related adverse events (irAE) in epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). Now that PD-(L)1 inhibitors are routinely used as adjuvant and first-line treatments, sequential PD-(L)1 inhibition followed by osimertinib use may become more frequent and have unforeseen serious toxicity.
Positive Correlation of Peripheral CD8+ T Lymphocytes with Immune-Related Adverse Events and Combinational Prognostic Value in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors. [2023]Immune checkpoint inhibitors (ICIs) therapy has revolutionized the treatment patterns of non-small cell lung cancer (NSCLC). However, patients treated with ICIs may experience immune-related adverse events (irAEs). Markers that could predict the onset of irAEs are still unclear. Here, we report the possible correlation of baseline peripheral lymphocytes with irAEs and clinical outcomes in advanced NSCLC patients receiving ICIs. A total of 109 advanced NSCLC patients treated with ICIs from April 2017 to January 2021 were analyzed retrospectively. Logistic and Cox regression analyses was applied to evaluate independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). Among these patients, 55 (50.5%) patients experienced irAEs. The level of CD8+ T lymphocytes at baseline was the independent risk factor for the onset of irAEs (p = 0.008). A higher level of CD8+ T lymphocytes was associated with longer PFS (11.0 months vs. 3.0 months, p
The safety of first and subsequent lines of PD-1/PD-L1 inhibitors monotherapy in non-small cell lung cancer patients: a meta-analysis. [2022]In both first or subsequent therapy of patients with non-small cell lung cancer (NSCLC), some programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors have shown prominent efficacy and safety. However, the disease spectra of side effects in different therapy time might exist heterogeneity. In this meta-analysis, we assessed and compared the safety of PD-1/PD-L1 inhibitors in first or subsequent line therapy. And the system-specific disease spectra of both treatment-related adverse events (trAEs) and immune-related adverse events (irAEs) were summarized.
Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies. [2022]The therapeutic use of anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab) is rapidly increasing. Given their mechanism of action that triggers T-cell activation, these immune checkpoint inhibitors induce specific adverse events that are mostly of immunologic origin. In this way, cutaneous toxicities represent the most frequent immune-related adverse events (irAEs). The purpose of this review is to summarize the most prevalent dermatologic complications induced by PD-1/PD-L1 immune checkpoint-blocking antibodies and to compare their dermatologic safety profile with anti-CTLA-4 ipilimumab.
Combined IL-2, agonistic CD3 and 4-1BB stimulation preserve clonotype hierarchy in propagated non-small cell lung cancer tumor-infiltrating lymphocytes. [2022]Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) yielded clinical benefit in patients with checkpoint blockade immunotherapy-refractory non-small cell lung cancer (NSCLC) prompting a renewed interest in TIL-ACT. This preclinical study explores the feasibility of producing a NSCLC TIL product with sufficient numbers and enhanced attributes using an improved culture method.
PD-1T TILs as a Predictive Biomarker for Clinical Benefit to PD-1 Blockade in Patients with Advanced NSCLC. [2023]Durable clinical benefit to PD-1 blockade in non-small cell lung cancer (NSCLC) is currently limited to a small fraction of patients, underlining the need for predictive biomarkers. We recently identified a tumor-reactive tumor-infiltrating T lymphocyte (TIL) pool, termed PD-1T TILs, with predictive potential in NSCLC. Here, we examined PD-1T TILs as biomarker in NSCLC.