Trial Summary
What is the purpose of this trial?This trial uses a special chemotherapy followed by the patient's own lab-grown immune cells and a drug to boost the immune system. It targets patients with advanced biliary tract cancers, which are difficult to treat. The process involves removing tumor cells, growing immune cells in a lab, reducing the patient's existing immune cells, and then infusing the lab-grown cells back into the patient.
What data supports the idea that TIL Therapy for Biliary Tract Cancer is an effective treatment?The available research does not provide specific data on TIL Therapy for Biliary Tract Cancer. However, it does mention other treatments like immune checkpoint inhibitors, which have shown promising results. For example, patients with advanced biliary tract cancers who received immunotherapy had a median survival of over 10 months, compared to just 2 months for those who received chemotherapy. This suggests that immunotherapy, which includes treatments like TIL Therapy, could be effective for biliary tract cancer.5691114
Is TIL Therapy a promising treatment for Biliary Tract Cancer?TIL Therapy, which uses Tumor Infiltrating Lymphocytes, is a promising treatment for Biliary Tract Cancer because it involves using the body's own immune cells to fight the cancer. This approach can potentially improve the body's ability to target and destroy cancer cells, offering hope for better outcomes.123712
What safety data exists for TIL therapy in biliary tract cancer?The provided research does not specifically address the safety data for TIL therapy, Lifileucel, or Amtagvi in biliary tract cancer. The studies focus on other immunotherapies and combinations, such as NK cells with pembrolizumab, local-regional therapy with toripalimab and lenvatinib, and immune checkpoint inhibitors. These studies generally report on the safety and efficacy of these treatments, noting adverse events but not specific toxicities. However, none of the studies directly evaluate TIL therapy for biliary tract cancer.48101113
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop your current medications. However, you must wait more than four weeks after any prior systemic therapy before starting the trial's preparative regimen, and your toxicities must have recovered to a manageable level.
Eligibility Criteria
This trial is for adults aged 18-75 with advanced, recurrent, or metastatic biliary tract cancers who have not responded to standard treatments. They must be able to handle specific chemotherapy and high-dose aldesleukin, sign informed consent, have an ECOG performance status of 0 or 1 (fully active or restricted in physically strenuous activity but ambulatory), and agree to birth control measures. Those with small, stable brain metastases may qualify.Inclusion Criteria
I am enrolled in HCC 17-220 and have TIL cultures ready for therapy.
My cancer has spread and does not respond to standard treatments like gemcitabine or cisplatin.
I have advanced or spreading cancer in my bile ducts, gallbladder, or nearby areas.
My cancer has spread and does not respond to standard treatments like gemcitabine or cisplatin.
My local cancer cannot be removed with standard surgery.
My cancer cannot be removed with standard surgery.
I am between 18 and 75 years old.
I am fully active or restricted in physically strenuous activity but can do light work.
I am enrolled in HCC 17-220 and have TIL cultures ready for therapy.
Exclusion Criteria
I do not have any active infections, bleeding disorders, or major illnesses.
My lung function is reduced, I've smoked heavily, and I have breathing problems.
I have a history of a serious autoimmune disease affecting major organs.
I am currently taking steroid medication.
I have had symptoms of heart disease.
Treatment Details
The study tests the effectiveness of Tumor Infiltrating Lymphocytes (TIL) therapy combined with a non-myeloablative lymphodepleting regimen followed by high-dose aldesleukin in patients with biliary tract cancer. It's a Phase 2 trial aiming to see if this approach can shrink tumors in those who haven't had success with other treatments.
1Treatment groups
Experimental Treatment
Group I: Tumor Infiltrating Lymphocytes (TIL)Experimental Treatment1 Intervention
Patients with locally advanced, recurrent, or metastatic biliary tract cancers will receive the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide, followed by infusion of up to 2x10\^11 lymphocytes 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 cell 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:
Allyson WelschPittsburgh, PA
UPMC Hillman Cancer CenterPittsburgh, PA
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Who is running the clinical trial?
Udai KammulaLead Sponsor
References
Liver tumor infiltrating lymphocytes: comparison of hepatocellular and cholangiolar carcinoma. [2021]To investigate the role of tumor infiltrating lymphocytes (TIL) in primary hepatocellular and cholangiolar carcinomas of the liver.
A phase II trial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma. [2022]Current data suggest that chemotherapy combinations may be superior to single agents in biliary tract cancer. The epidermal growth factor receptor (EGFR) pathway appears to be associated with tumor stage, prognosis and response to therapy. This trial was designed to evaluate the tolerability and efficacy of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan.
High ratio of programmed cell death protein 1 (PD-1)(+)/CD8(+) tumor-infiltrating lymphocytes identifies a poor prognostic subset of extrahepatic bile duct cancer undergoing surgery plus adjuvant chemoradiotherapy. [2018]This study investigated the prognostic role of PD-L1 expression, PD-1(+) tumor-infiltrating lymphocytes (TILs), and the ratio of PD-1(+)/CD8(+) TILs in extrahepatic bile duct (EHBD) cancer.
Current Progress in Immunotherapy for the Treatment of Biliary Cancers. [2018]Biliary tract cancers (BTC) remain one of the poorest groups of malignancies in terms of long-term survival, with only limited success in improvements by the use of systemic chemotherapy and our current repertoire of molecularly targeted therapies. Treatments that aim to adapt the patient's own immune system to target cancer cell have shown tremendous promise in treating solid tumors such as melanoma and non-small cell lung cancer, and there are many recently completed and ongoing studies looking to move immunotherapy into the treatment of BTC. We review here both preclinical and early clinical studies of immune therapies for BTC, including autologous cell transfer, vaccinations, and immunomodulatory approaches (e.g., immune checkpoint inhibitors).
Immunotherapy as a treatment for biliary tract cancers: A review of approaches with an eye to the future. [2019]Biliary tract cancers (BTC) are aggressive malignancies associated with resistance to chemotherapy and poor prognostic rates. Therefore, novel treatment approaches are in need. Immunotherapy represents a promising breakthrough that uses a patient's immune system to target a tumor. This treatment approach has shown immense progress with positive results for selected cancers such as melanoma and nonsmall cell lung cancer. Initial preclinical data and preliminary clinical studies suggest encouraging mechanistic effects for immunotherapy in BTC offering the hope for an expanding therapeutic role for this disease. These approaches include targeted tumor antigen therapy via peptide and dendritic cell-based vaccines, allogenic cell adoptive immunotherapy, and the use of inhibitory agents targeting the immune checkpoint receptor pathway and multiple components of the tumor microenvironment. At this time demonstrating efficacy in larger clinical trials remains imperative. A multitude of ongoing trials aim to successfully translate mechanistic effects into antitumor efficacy and ultimately aim to incorporate immunotherapy into the routine management of BTC. With further research efforts, the optimization of dosing and therapeutic regimens, the identification of novel tumor antigens and a better understanding of alternative checkpoint pathway receptor expression may provide additional targets for rational combinatorial therapies which enhance the effects of immunotherapy and may offer hope for further advancing treatment options. Ultimately, the challenge remains to prospectively identify the subsets of patients with BTC who may respond to immunotherapy, and devising alternative strategies to sensitize those that do not with the hopes of improving outcomes for all with this deadly disease.
Reduction of immunosuppressive tumor microenvironment in cholangiocarcinoma by ex vivo targeting immune checkpoint molecules. [2020]Cholangiocarcinoma is an aggressive hepatobiliary malignancy originating from biliary tract epithelium. Whether cholangiocarcinoma is responsive to immune checkpoint antibody therapy is unknown, and knowledge of its tumor immune microenvironment is limited. We aimed to characterize tumor-infiltrating lymphocytes (TILs) in cholangiocarcinoma and assess functional effects of targeting checkpoint molecules on TILs.
Preoperative Neutrophil-to-lymphocyte Ratio Predicts Tumor-infiltrating CD8+ T Cells in Biliary Tract Cancer. [2020]Label="BACKGROUND/AIM" NlmCategory="OBJECTIVE">This study evaluated the prognostic significance of preoperative neutrophil-to-lymphocyte ratio (NLR) and CD8+ tumor-infiltrating lymphocytes (TILs), and whether preoperative NLR was associated with CD8+ TILs in biliary tract cancers (BTCs).
Efficacy and biomarker analysis of nivolumab plus gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers: results from a phase II study. [2022]The prognosis of patients with unresectable or metastatic biliary tract cancer (BTC) is unacceptably low. This study aimed to determine the efficacy, safety and predictive biomarkers of the immune checkpoint inhibitor nivolumab in combination with chemotherapy in advanced BTCs.
Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. [2021]Systemic therapies for metastatic biliary tract cancers are few, and patients have a median overall survival of less than 1 year. MyPathway evaluates the activity of US Food and Drug Administration-approved therapies in non-indicated tumours with potentially actionable molecular alterations. In this study, we present an analysis of patients with metastatic biliary tract cancers with HER2 amplification, overexpression, or both treated with a dual anti-HER2 regimen, pertuzumab plus trastuzumab, from MyPathway.
Safety and Efficacy of Allogeneic Natural Killer Cells in Combination with Pembrolizumab in Patients with Chemotherapy-Refractory Biliary Tract Cancer: A Multicenter Open-Label Phase 1/2a Trial. [2022]This study investigated the administration of combination therapy, allogeneic natural killer (NK) cells and pembrolizumab in the treatment of advanced biliary tract cancer to determine the safety and tolerability (phase 1) and the efficacy and safety (phase 2a).
The efficiency and safety of immune checkpoint inhibitors for advanced biliary tract cancers based on gene profiles: A retrospectively controlled study. [2022]Immune checkpoint inhibitors are potential agents to improve the survival of advanced biliary tract cancers (ABTCs). The current results are controversial because the predictors are imprecise. We present our primary experience with ABTCs based on gene landscape with exciting outcomes. ABTCs who were admitted to The First Affiliated Hospital of Henan University of Science and Technology from October 2019 to March 2021 were enrolled. They were divided into chemotherapy group or immunotherapy group according to the treatment. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were response and toxicities. SSPS 16.0 was used for statistical analysis. A total of 33 patients were enrolled, including 25 in the chemotherapy group and 8 in the immunotherapy group. The median OS and PFS of the chemotherapy group were 2 and 4 months, respectively. The estimated median OS and PFS of immunotherapy were 10 + and 10 + months, respectively. The differences of OS and PFS between the 2 groups were significant (P = .000; P = .003). Stratified analysis showed that these differences were mainly from those patients with high expression of PD-L1 > 10%. The difference in the overall response was significant between 2 groups (χ2 = 9.275; P = .026). The difference in adverse events between the 2 groups was not significant. Immune checkpoint inhibitors were effective and safe for ABTCs with high expression of PD-L1. The threshold should be precise.
Tumor-infiltrating lymphocytes and macrophages as a significant prognostic factor in biliary tract cancer. [2023]The impact of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) on the prognosis of biliary tract cancer (BTC) is not completely understood. Therefore, in our study, we investigated the effects of the various immune cells infiltration in tumor microenvironment (TME).
Local-regional therapy combined with toripalimab and lenvatinib in patients with advanced biliary tract cancer. [2023]Local-regional therapy combined with PD-1 inhibitors and lenvatinib (triple combination therapy) has demonstrated potent antitumor activity in solid tumors. However, the efficacy and safety of the triple combination therapy in patients with advanced biliary tract cancer (BTC) remain unclear. This retrospective study evaluated the efficacy and safety of the triple combination therapy in advanced BTC. Tumor tissues were collected to assess the expression status of PDL1 to identify efficacy biomarkers. Forty-nine patients were included: 24 in lenvatinib plus toripalimab therapy; 25 in the triple combination therapy. The triple combination therapy group showed longer median progression-free survival (mPFS) (7.9 versus 5.6 months, P=0.015) and longer median overall survival (mOS) (13.7 versus 11.1 months, P=0.145) than the lenvatinib plus toripalimab group. The overall response rate (ORR) was 32% [95% confidence interval (CI): 12.3-51.7] with the triple combination therapy versus 25% (95% CI: 6.3-43.7) with toripalimab plus lenvatinib. Three patients received surgery after the triple combination therapy. All patients experienced any-grade adverse events (AEs) without any specific toxicities. PDL1 expression was associated with improved clinical benefits. Local-regional therapy combined with PD-1 inhibitors and lenvatinib may be an encouraging treatment choice for advanced BTC without an increase in specific toxicities.
Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study. [2023]To evaluate the efficacy and safety of tucatinib and trastuzumab in patients with previously treated human epidermal growth factor receptor 2-positive (HER2+) metastatic biliary tract cancer (mBTC).