T Cell Immunotherapy for Lung Cancer

Recruiting at 1 trial location

Overseen By NCI SB Immunotherapy Recruitment Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Steroids

Disqualifiers: Nursing, Immunosuppression, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

85 Participants Needed

Trial Summary

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, you must have completed any prior systemic therapy before enrolling, and you cannot be on ongoing immunosuppressive drugs, including steroids.

What data supports the effectiveness of the treatment Young TIL for lung cancer?

Research shows that tumor-infiltrating lymphocytes (TILs) can recognize and destroy cancer cells in lung cancer, and a study found that TIL treatment led to tumor reduction in patients with advanced lung cancer. Additionally, TIL therapy has shown success in treating other cancers like melanoma, suggesting its potential effectiveness in lung cancer. ^{1 2 3 4 5}

Is T Cell Immunotherapy for Lung Cancer safe for humans?

Research on T Cell Immunotherapy, including Tumor Infiltrating Lymphocytes (TIL) and Young TIL, has shown promising results in treating conditions like melanoma and lung cancer. While these studies focus on effectiveness, they also suggest that the treatment process is generally safe, as it involves using the patient's own immune cells, which are expanded and reintroduced to fight cancer. ^{5 6 7 8 9}

How is the Young TIL treatment for lung cancer different from other treatments?

Young TIL treatment is unique because it uses the patient's own immune cells, specifically T cells that have infiltrated the tumor, to fight cancer. These cells are collected, expanded in the lab, and then reintroduced into the patient to enhance the body's natural ability to target and destroy cancer cells, offering a personalized approach compared to traditional chemotherapy or radiation. ^{1 5 10 11 12}

What is the purpose of this trial?

Background: The NCI Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 100 patients. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells. Objective: The purpose of this study is to see if these specifically selected tumor fighting cells can cause non-small cell lung cancer (NSCLC) tumors to shrink and to see if this treatment is safe. Eligibility: - Adults age 18-72 with NSCLC who have a tumor that can be safely removed. Design: * Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed * Surgery: If the patients meet all of the requirements for the study they will undergo surgery to remove a tumor that can be used to grow the TIL product. * Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.} * Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.

Research Team

James C Yang, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults aged 18-72 with advanced non-small cell lung cancer (NSCLC) who've had prior treatment and have a tumor that can be removed. They must not have HIV, active hepatitis B or C, and agree to use birth control. Excluded are those on other trials, breastfeeding women, people needing steroids, with major medical issues, severe allergies to study drugs or certain heart/lung conditions.

Inclusion Criteria

I am willing to use birth control during and after my treatment.

Your blood counts need to be within normal ranges: ANC (a type of white blood cell) should be higher than 1000, WBC (white blood cell) count should be higher than 2500, Hb (hemoglobin) should be higher than 8.0, and platelet count should be higher than 80,000.

My lung cancer is advanced but has a part that can be removed for treatment.

Exclusion Criteria

You have a condition that weakens your immune system from birth.

History of severe immediate hypersensitivity reaction to any of the agents used in this study

Women who are breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Work up stage

Patients undergo history and physical examination, scans, x-rays, lab tests, and other tests as needed

1-2 weeks

1-2 visits (in-person)

Surgery and Leukapheresis

Patients undergo surgery to remove a tumor and may undergo leukapheresis to obtain additional white blood cells

1 week

1 visit (in-person)

Treatment

Patients receive conditioning chemotherapy, TIL cells, and aldesleukin, staying in the hospital for about 4 weeks

4 weeks

Inpatient stay

Follow-up

Patients return for physical exams, review of side effects, lab tests, and scans every 1-3 months for the first year, then every 6 months to 1 year

Up to 2 years

Multiple visits (in-person)

Treatment Details

Interventions

• Young TIL

Trial Overview The trial is testing Tumor Infiltrating Lymphocytes (TIL) therapy in NSCLC patients. This involves removing the patient's tumor cells, growing specific white blood cells from them in a lab and infusing them back into the patient along with chemotherapy drugs Cyclophosphamide and Fludarabine followed by Aldesleukin.

Participant Groups

Group I: 2/Low-Dose Aldesleukin Experimental Treatment 4 Interventions

Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine plus young TIL plus low-dose Aldesleukin

Group II: 1/High-Dose Aldesleukin Experimental Treatment 4 Interventions

Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine plus young TIL plus high-dose Aldesleukin

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study involving 70 samples from patients with advanced non-small cell lung carcinoma (NSCLC), 46 samples of tumor-infiltrating lymphocytes (TIL) were successfully expanded in vitro, producing between 10 to 50 billion cells that effectively targeted and killed the patients' own cancer cells.

The TILs showed a preselected oligoclonal population that could be expanded while retaining their cancer-fighting properties, suggesting a promising approach for adoptive immunotherapy in patients with residual NSCLC after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation and in vitro expansion of lymphocytes infiltrating non-small cell lung carcinoma: functional and molecular characterisation for their use in adoptive immunotherapy. Melioli, G., Ratto, G., Guastella, M., et al.[2019]

A study analyzing 12,346 T cells from 14 treatment-naïve non-small-cell lung cancer patients revealed that a higher ratio of 'pre-exhausted' to exhausted CD8+ T cells is linked to better prognosis, suggesting that these pre-exhausted cells may retain more functional potential.

The research also identified distinct populations of tumor regulatory T cells (Tregs) with specific gene signatures, where activated Tregs correlated with poorer outcomes, indicating their role in tumor progression and potential as targets for therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing. Guo, X., Zhang, Y., Zheng, L., et al.[2022]

In a phase 1 trial involving 20 patients with advanced non-small cell lung cancer, adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) combined with nivolumab was found to be generally safe, meeting the safety criteria with a severe toxicity rate of ≤17%.

Of the 13 evaluable patients, 3 showed confirmed responses to the treatment, and 11 experienced a reduction in tumor burden, indicating that TIL therapy may be an effective new strategy for treating metastatic lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial. Creelan, BC., Wang, C., Teer, JK., et al.[2023]

Tumor-infiltrating lymphocytes (TIL) were found in about 23% of 1,290 patients with resected lung neoplasms, being significantly more common in non-small cell lung carcinomas compared to neuroendocrine tumors.

The presence of TIL is associated with improved survival in patients with squamous cell carcinomas, especially in early-stage disease, with the survival benefit becoming more pronounced over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical significance of tumor-infiltrating lymphocytes in lung neoplasms. Ruffini, E., Asioli, S., Filosso, PL., et al.[2022]

In patients with non-small cell lung cancer (NSCLC), tumor-infiltrating lymphocytes (TILs) show a distinct composition, with CD8 T cells being more prevalent in naive TILs, while CD4 T cells dominate in memory TILs, indicating different roles in immune response.

The study found that naive-phenotype T cells in TILs produce high levels of cytokines like IFN-γ and TNF-α, and that stem cell-like memory T cells (Tscm) are promising candidates for adoptive cell therapy due to their strong cytokine production and unique characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Characteristics of Naive-like T Cells in Tumor-infiltrating Lymphocytes From Human Lung Cancer. Sheng, SY., Gu, Y., Lu, CG., et al.[2022]

Adoptive transfer of Young tumor infiltrating lymphocytes (TIL) has shown a 48% clinical response rate in metastatic melanoma patients, with 15 out of 31 evaluated patients achieving either complete or partial responses.

The process for generating Young-TIL is efficient, with cultures established in about 16.7 days for 93% of enrolled patients, suggesting that this method could be widely adopted by cancer centers to improve treatment accessibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment and large-scale expansion of minimally cultured "young" tumor infiltrating lymphocytes for adoptive transfer therapy. Itzhaki, O., Hovav, E., Ziporen, Y., et al.[2018]

The study found that the majority of tumor-infiltrating lymphocytes (TIL) in lung cancer are activated memory T-cells, indicating a potential immune response to tumor cells.

However, the effectiveness of these TILs is compromised due to a lack of interleukin-2 (IL-2) and suppression from factors released by lung cancer cells, which limits their ability to respond to tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-reactive T-cells accumulate in lung cancer tissues but fail to respond due to tumor cell-derived factor. Yoshino, I., Yano, T., Murata, M., et al.[2017]

The TIL 3.0 method, which uses IL-2 combined with agonistic antibodies, significantly enhances the expansion of tumor-infiltrating lymphocytes (TIL) from non-small cell lung cancer (NSCLC) tumors, producing 5.3 times more TIL compared to the traditional TIL 1.0 method.

TIL 3.0 not only increases the quantity of CD8+ TIL but also maintains a diverse T-cell repertoire that closely resembles the original tumor's clonal hierarchy, suggesting a greater potential for effective adoptive cell transfer therapies in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined IL-2, agonistic CD3 and 4-1BB stimulation preserve clonotype hierarchy in propagated non-small cell lung cancer tumor-infiltrating lymphocytes. Shah, P., Forget, MA., Frank, ML., et al.[2022]

Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) has been successfully established from tumor specimens of five non-small cell lung cancer (NSCLC) patients, showing promise for treating this type of cancer.

The TIL cultures from lung cancer patients demonstrated similar growth and characteristics to those from melanoma patients, indicating that TIL ACT could be a viable new treatment option for metastatic NSCLC, with plans for a clinical trial to follow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment of adoptive cell therapy with tumor infiltrating lymphocytes for non-small cell lung cancer patients. Ben-Avi, R., Farhi, R., Ben-Nun, A., et al.[2019]

In a study of 100 non-small-cell lung cancer (NSCLC) patients followed for 3 years, higher T-cell infiltration was associated with better survival outcomes, indicating that T-cell presence may play a crucial role in fighting the cancer.

Specifically, patients in the survival group had a significantly higher rate of CD8+ T-cell infiltration (72.1%) compared to those in the death group (47.6%), suggesting that these T-cells are important for anti-tumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Effect of T Lymphocytes Infiltrated by Tumors on Non-Small-Cell Lung Cancer. Sheng, S., Lu, C., Guo, J., et al.[2022]

In a study of 218 patients with non-small-cell lung cancer (NSCLC), a high ratio of FOXP3+ to CD4+ T cells was found to be a poor prognostic factor for overall and recurrence-free survival, particularly in patients with adenocarcinoma.

For non-adenocarcinoma patients, a low number of CD8+ T cells was associated with worse outcomes, highlighting the importance of T-cell types in predicting survival based on histological type and smoking habits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic value of tumor-infiltrating lymphocytes differs depending on histological type and smoking habit in completely resected non-small-cell lung cancer. Kinoshita, T., Muramatsu, R., Fujita, T., et al.[2022]

In a study of 178 non-small cell lung cancer (NSCLC) patients, higher levels of CD8(+) T cells within tumor nests were associated with shorter survival times, indicating that these cells may not effectively combat the tumor.

Conversely, higher numbers of CD4(+) T cells in the surrounding stroma correlated with longer survival, suggesting that these cells may play a protective role against cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers. Wakabayashi, O., Yamazaki, K., Oizumi, S., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Isolation and in vitro expansion of lymphocytes infiltrating non-small cell lung carcinoma: functional and molecular characterisation for their use in adoptive immunotherapy. [2019]

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

Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing. [2022]

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

Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical significance of tumor-infiltrating lymphocytes in lung neoplasms. [2022]

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

The Characteristics of Naive-like T Cells in Tumor-infiltrating Lymphocytes From Human Lung Cancer. [2022]

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

Establishment and large-scale expansion of minimally cultured "young" tumor infiltrating lymphocytes for adoptive transfer therapy. [2018]

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

Tumor-reactive T-cells accumulate in lung cancer tissues but fail to respond due to tumor cell-derived factor. [2017]

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

Combined IL-2, agonistic CD3 and 4-1BB stimulation preserve clonotype hierarchy in propagated non-small cell lung cancer tumor-infiltrating lymphocytes. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Establishment of adoptive cell therapy with tumor infiltrating lymphocytes for non-small cell lung cancer patients. [2019]

10. Egypt pubmed.ncbi.nlm.nih.gov

Immune Effect of T Lymphocytes Infiltrated by Tumors on Non-Small-Cell Lung Cancer. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Prognostic value of tumor-infiltrating lymphocytes differs depending on histological type and smoking habit in completely resected non-small-cell lung cancer. [2022]

12. England pubmed.ncbi.nlm.nih.gov

CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers. [2022]