TIL Therapy for Biliary Tract Cancer

Recruiting at1 trial location

Overseen by Udai S Kammula, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Udai Kammula

Must not be taking: Steroids, Anti-infectives

Disqualifiers: Pregnancy, Immunodeficiency, Infections, others

No Placebo Group

Prior Safety Data

Approved in 1 Jurisdiction

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that more than four weeks must have passed since any prior systemic therapy before starting the preparative regimen. This suggests a possible need to pause certain treatments.

What data supports the effectiveness of the treatment Tumor Infiltrating Lymphocytes (TIL), Lifileucel, Amtagvi for biliary tract cancer?

Research on immune checkpoint inhibitors, which are a type of immunotherapy like TIL therapy, shows promising results for advanced biliary tract cancers, with significantly longer survival times compared to traditional chemotherapy. This suggests that treatments harnessing the immune system, such as TIL therapy, may offer hope for improving outcomes in biliary tract cancer. ^{1 2 3 4 5}

Is TIL therapy safe for humans?

There is no specific safety data available for TIL therapy in biliary tract cancer, but similar immune therapies have been studied and found to be generally safe in humans for other conditions. ^{2 6 7 8 9}

How is TIL therapy different from other treatments for biliary tract cancer?

TIL therapy for biliary tract cancer is unique because it uses the patient's own immune cells, specifically tumor-infiltrating lymphocytes, to fight the cancer, which is different from traditional chemotherapy that uses drugs to kill cancer cells. ^{10 11 12 13 14}

Research Team

Udai S Kammula, MD

Principal Investigator

UPMC Hillman Cancer Center

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

Able to understand and sign the Informed Consent Document

I agree to use birth control during and up to four months after the study.

I am enrolled in HCC 17-220 and have TIL cultures ready for therapy.

Exclusion Criteria

You have had a serious allergic reaction to any of the medications used in this study in the past.

You are not currently taking any other experimental drugs or treatments.

I do not have any active infections, bleeding disorders, or major illnesses.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Preparation

Patients undergo resection or biopsy of tumor to obtain Tumor Infiltrating Lymphocytes (TIL) for growth and expansion.

Variable

Treatment

Participants receive a 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 after treatment.

Up to 24 months

Treatment Details

Interventions

• Tumor Infiltrating Lymphocytes (TIL) (CAR T-cell Therapy)

Trial Overview 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.

Participant Groups

Group I: Tumor Infiltrating Lymphocytes (TIL) Experimental Treatment 1 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.

Who Is Running the Clinical Trial?

Udai Kammula

Lead Sponsor

Trials

3

Recruited

350+

Findings from Research

In a study of 30 patients with previously treated HER2-positive metastatic biliary tract cancer, the combination of tucatinib and trastuzumab showed a confirmed objective response rate of 46.7%, indicating significant antitumor activity.

The treatment was generally well tolerated, with common side effects including fever and diarrhea, but no deaths were attributed to treatment-related adverse events, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study. Nakamura, Y., Mizuno, N., Sunakawa, Y., et al.[2023]

The combination therapy of allogeneic natural killer (NK) cells and pembrolizumab was found to be safe, with no severe adverse events directly related to the treatment in phase 1, and only 47.1% of patients in phase 2a experiencing severe adverse events.

This treatment showed promising antitumor activity, achieving an overall response rate of 17.4% in the full analysis set and 50.0% in the per-protocol set, indicating improved efficacy compared to pembrolizumab alone in patients with advanced biliary tract cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Leem, G., Jang, SI., Cho, JH., et al.[2022]

In a study of 49 patients with advanced biliary tract cancer, the triple combination therapy of local-regional treatment, PD-1 inhibitors, and lenvatinib resulted in a longer median progression-free survival (7.9 months) compared to lenvatinib plus toripalimab alone (5.6 months).

The overall response rate for the triple combination therapy was 32%, indicating promising efficacy, and importantly, this treatment did not lead to increased specific toxicities, making it a potentially safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local-regional therapy combined with toripalimab and lenvatinib in patients with advanced biliary tract cancer. Wang, Y., Xun, Z., Yang, X., et al.[2023]

In a phase II trial involving 32 patients with advanced biliary tract cancer, the combination of nivolumab with gemcitabine and cisplatin resulted in a 55.6% objective response rate, indicating promising efficacy for this treatment approach.

The treatment was generally safe, with manageable side effects; however, the most common severe adverse events included thrombocytopenia (56%) and neutropenia (22%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Feng, K., Liu, Y., Zhao, Y., et al.[2022]

Biliary tract cancers (BTC) have poor long-term survival rates, and while systemic chemotherapy and targeted therapies have had limited success, immunotherapy shows promise as a potential treatment option.

Current research includes various immunotherapy approaches such as autologous cell transfer and immune checkpoint inhibitors, with ongoing studies aimed at improving treatment outcomes for BTC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Progress in Immunotherapy for the Treatment of Biliary Cancers. Pauff, JM., Goff, LW.[2018]

In a study of 130 patients with biliary tract cancer, a high Immunoscore, based on the presence of specific immune cells, was associated with significantly better overall survival (60.8 months vs. 26.4 months) and recurrence-free survival compared to a low Immunoscore.

The high Immunoscore was identified as an independent prognostic factor for both overall survival and recurrence-free survival, indicating its potential as a valuable marker in assessing patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-infiltrating lymphocytes and macrophages as a significant prognostic factor in biliary tract cancer. Tanaka, R., Eguchi, S., Kimura, K., et al.[2023]

In a study of 35 liver cancer specimens, both hepatocellular and cholangiolar carcinomas showed significant infiltration of tumor-infiltrating lymphocytes (TIL), particularly CD4+ T cells at the tumor/liver interface and CD8+ T cells within the tumor itself.

The presence of these lymphocytes suggests they may play distinct roles in the immune response against liver tumors, although their distribution and quantity did not differ significantly between the two types of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver tumor infiltrating lymphocytes: comparison of hepatocellular and cholangiolar carcinoma. Kasper, HU., Drebber, U., Stippel, DL., et al.[2021]

In a study of 83 patients with extrahepatic bile duct (EHBD) cancer, a higher ratio of PD-1(+) to CD8(+) tumor-infiltrating lymphocytes (TILs) was linked to significantly poorer overall survival, relapse-free survival, and distant metastasis-free survival, indicating its potential as a critical prognostic factor.

The findings suggest that targeting the immune checkpoint pathways, particularly in patients with a high PD-1(+)/CD8(+) TIL ratio, could enhance treatment outcomes when combined with conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Lim, YJ., Koh, J., Kim, K., et al.[2018]

In a study of 154 patients with biliary tract cancers, a high preoperative neutrophil-to-lymphocyte ratio (NLR) was linked to shorter overall survival (OS) and recurrence-free survival (RFS), indicating it may serve as a negative prognostic factor.

Conversely, a high level of CD8+ tumor-infiltrating lymphocytes (TILs) was associated with longer OS and RFS, suggesting that these immune cells may play a protective role against cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative Neutrophil-to-lymphocyte Ratio Predicts Tumor-infiltrating CD8+ T Cells in Biliary Tract Cancer. Tanaka, R., Kimura, K., Eguchi, S., et al.[2020]

The combination of panitumumab with gemcitabine and irinotecan showed promising efficacy in treating advanced cholangiocarcinoma, achieving a 5-month progression-free survival (PFS) rate of 69% and a median PFS of 9.7 months among 35 patients.

The treatment was generally well-tolerated, with a disease-control rate of 74% and manageable side effects, indicating that this regimen could be a viable option for patients with unresectable or metastatic biliary tract cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma. Sohal, DP., Mykulowycz, K., Uehara, T., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

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]

2. United States pubmed.ncbi.nlm.nih.gov

The efficiency and safety of immune checkpoint inhibitors for advanced biliary tract cancers based on gene profiles: A retrospectively controlled study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Immunotherapy as a treatment for biliary tract cancers: A review of approaches with an eye to the future. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Reduction of immunosuppressive tumor microenvironment in cholangiocarcinoma by ex vivo targeting immune checkpoint molecules. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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]

7. United States pubmed.ncbi.nlm.nih.gov

Local-regional therapy combined with toripalimab and lenvatinib in patients with advanced biliary tract cancer. [2023]

8. England pubmed.ncbi.nlm.nih.gov

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]

9. United States pubmed.ncbi.nlm.nih.gov

Current Progress in Immunotherapy for the Treatment of Biliary Cancers. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Tumor-infiltrating lymphocytes and macrophages as a significant prognostic factor in biliary tract cancer. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Liver tumor infiltrating lymphocytes: comparison of hepatocellular and cholangiolar carcinoma. [2021]

12. Ireland pubmed.ncbi.nlm.nih.gov

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]

13. Greece pubmed.ncbi.nlm.nih.gov

Preoperative Neutrophil-to-lymphocyte Ratio Predicts Tumor-infiltrating CD8+ T Cells in Biliary Tract Cancer. [2020]

14. England pubmed.ncbi.nlm.nih.gov

A phase II trial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma. [2022]