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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an experimental treatment called Young TIL for non-small cell lung cancer (NSCLC) to determine its ability to shrink tumors and ensure safety. The treatment uses special white blood cells taken from a patient's tumor, grown in the lab, and then returned to the patient to combat the cancer. The trial seeks participants with NSCLC that cannot be surgically removed and who have undergone at least one previous treatment. Participants must have a tumor that can be safely removed for this process. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TIL (Tumor Infiltrating Lymphocyte) therapy is generally well-tolerated by patients with non-small cell lung cancer (NSCLC). Studies have found that about 63% of patients experienced stable disease, meaning their cancer did not worsen, indicating some level of safety and effectiveness. Additionally, about 30-35% of patients saw a more significant positive response, with their tumors shrinking.

This treatment is a type of immunotherapy. It involves extracting specific white blood cells from the patient's tumor, multiplying them, and then reintroducing them to the patient. This process often includes a drug called aldesleukin, administered in low or high doses. Chemotherapy drugs like cyclophosphamide and fludarabine are also commonly used as part of the treatment.

While no serious safety issues have emerged, it's important to note that this therapy can have side effects, especially when combined with chemotherapy and aldesleukin. As a Phase 2 trial, the treatment has been tested in a moderate number of patients, providing some safety data, though not as extensive as in later phases. Those interested in joining should consult their doctors to better understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about T Cell Immunotherapy for lung cancer because it harnesses the power of young tumor-infiltrating lymphocytes (TILs) to target and destroy cancer cells. Unlike traditional treatments like chemotherapy and radiation, which can damage healthy cells, this therapy aims to boost the body's own immune response specifically against cancer. The trial is exploring two dosing strategies with Aldesleukin, a drug that further stimulates immune cell activity. This approach could potentially offer a more precise and less harmful alternative to current lung cancer treatments, with the possibility of enhanced effectiveness and fewer side effects.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that Tumor Infiltrating Lymphocyte (TIL) therapy could effectively treat non-small cell lung cancer (NSCLC). In this trial, participants will receive TIL therapy combined with either low-dose or high-dose aldesleukin. Studies have demonstrated that TIL combined with low-dose aldesleukin achieved a disease control rate of 80% and an overall response rate (ORR) of 36%, indicating that many patients experienced tumor shrinkage or halted growth. TIL with high-dose aldesleukin also produced lasting and significant results, suggesting it may help manage the disease over time. This treatment uses the patient's own immune cells to fight the cancer, offering a unique and promising approach. Both treatments aim to harness the body's natural defenses to effectively target and reduce tumor size. ^{2 5 6 7 8}

Who Is on the Research Team?

James C Yang, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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.

Willing to sign a durable power of attorney

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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 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]

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]

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 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]

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]

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]

Citations

1. astctjournal.org astctjournal.org/article/S2666-6367(24)00783-8/fulltext

Tumor-Infiltrating Lymphocyte Therapy: A New Frontier This trial indicated that TIL therapy could achieve durable and meaningful responses in NSCLC, including in the important subset of never-smoker lung cancer ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02621021

NCT02621021 | A Phase 2 Trial for Metastatic Melanoma ... Cell therapy is an experimental cancer therapy. It takes young tumor infiltrating lymphocytes (Young TIL) cells from a person s tumors and grows them in a lab.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10669950/

Tumor-Infiltrating Lymphocytes and Adoptive Cell Therapy These cells have proven prognostic and therapeutic value for many cancer outcomes and potential to treat also disseminated breast, colorectal, or lung cancer.

4. withpower.com withpower.com/trial/phase-3-carcinoma-9-2014-1eaba

T Cell Immunotherapy for Lung Cancer 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 ...

5. jitc.bmj.com jitc.bmj.com/content/12/2/e006822

Efficacy and safety of autologous tumor-infiltrating ... Tumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12274268/

Tumor infiltration therapy: from FDA approval to next ... ORRs of ~ 30–35% have been reported in this hard-to-treat population. Non-Small Cell Lung Cancer (NSCLC). Preliminary studies show promise, with ...

7. advanced.onlinelibrary.wiley.com advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202409356

TIL Therapy in Lung Cancer: Current Progress and Perspectives Unveiling the promise of Tumor-Infiltrating Lymphocytes (TIL) therapy for lung cancer treatment. This review introduces why TIL therapy is ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2666636724007838

Tumor-Infiltrating Lymphocyte Therapy: A New Frontier This review provides a summary of the latest advances in TIL therapy and what lies ahead for the field.