Autologous LN-145 for Lung Cancer

Recruiting at44 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Iovance Biotherapeutics, Inc.

Must be taking: Platinum-based chemotherapy

Must not be taking: Systemic steroids

Disqualifiers: Brain metastases, Organ transplant, others

No Placebo Group

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests LN-145, a treatment using a patient's own lab-prepared immune cells, in patients with advanced lung cancer that has spread. The process includes reducing existing immune cells, infusing enhanced ones, and boosting their activity.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude patients on systemic steroid therapy of 10 mg/day or more of prednisone or equivalent. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment LN-145 for lung cancer?

Research shows that tumor-infiltrating lymphocytes (TILs), like those used in LN-145, can recognize and destroy cancer cells in lung cancer and other types of cancer. Studies have demonstrated that TILs can be expanded in the lab and have shown strong anti-tumor effects, especially when combined with interleukin-2, a substance that helps boost the immune response. ^{1 2 3 4 5}

Is Autologous LN-145 safe for use in humans?

Safety data from studies on lifileucel (another name for LN-145) in patients with advanced melanoma showed that the treatment was generally safe, with no treatment-related deaths reported. The safety profile was consistent with known effects of lymphodepletion (a process to reduce white blood cells) and high-dose interleukin-2 (a type of immune system booster). ^{1 6 7 8 9}

How is the treatment LN-145 unique for lung cancer?

LN-145 is a unique treatment for lung cancer because it uses a patient's own immune cells, called tumor-infiltrating lymphocytes (TILs), which are expanded outside the body and then reintroduced to help fight the cancer. This approach is different from traditional treatments like chemotherapy and radiation, as it specifically targets the cancer cells using the body's immune system. ^{1 3 6 10 11}

Research Team

Iovance Biotherapeutics Study Team

Principal Investigator

Iovance Biotherapeutics

Eligibility Criteria

This trial is for adults with Stage IV non-small-cell lung cancer (NSCLC) without certain genetic mutations. Participants must have had disease progression after first-line therapy, be in good physical condition (ECOG status of 0 or 1), and have at least one tumor that can be surgically removed for treatment development. They should not have more than two prior lines of therapy and must agree to use effective birth control.

Inclusion Criteria

My lung cancer is stage IV and does not have EGFR, ALK, or ROS mutations.

I am fully active or can carry out light work.

I am over 70 and have discussed joining the trial with the Medical Monitor.

Exclusion Criteria

You had an organ transplant from another person or cell therapy in the last 20 years.

I am taking 10 mg or more of prednisone daily or its equivalent.

Participation in another interventional clinical study within 21 days

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a non-myeloablative lymphodepleting preparative regimen, followed by infusion of autologous TIL, and administration of IL-2

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

Retreatment

Patients previously treated with LN-145 may receive additional treatment

Treatment Details

Interventions

• LN-145 (CAR T-cell Therapy)

Trial Overview The study is testing LN-145, a new potential treatment developed from the patient's own immune cells. It's an open-label phase 2 trial, meaning both researchers and participants know what treatment is being given, focusing on those with metastatic NSCLC who meet specific criteria.

Participant Groups

Group I: Retreatment Cohort Experimental Treatment 1 Intervention

Patients who were previously treated with LN-145 in Cohort 1, 2, 3, or 4.

Group II: Cohort 4 Experimental Treatment 1 Intervention

Patients, regardless of tumor PD-L1 expression status prior to ICI treatment, who have meet all inclusion/exclusion criteria except the requirement to have documented disease progression may elect to have the tumor harvest procedure and TIL production prior to disease progression on their current anticancer treatment. Documentation of progressive disease and identification of a target lesion for RECIST v1.1 assessment is required at Baseline for these patients.

Group III: Cohort 3 Experimental Treatment 1 Intervention

Patients, regardless of tumor PD-L1 TPS prior to ICI treatment, who are unable to safely undergo a surgical tumor resection for TIL generation

Group IV: Cohort 2 Experimental Treatment 1 Intervention

Patients whose tumors expressed PD-L1 TPS ≥1% prior to ICI treatment

Group V: Cohort 1 Experimental Treatment 1 Intervention

Patients whose tumors did not express programmed cell death-ligand 1 (PD-L1), i.e., tumor proportion score (TPS) \< 1% prior to ICI treatment and Patients with no available historical TPS for PD-L1 expression

Who Is Running the Clinical Trial?

Iovance Biotherapeutics, Inc.

Lead Sponsor

Trials

26

Recruited

1,800+

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]

Tumor-infiltrating lymphocytes (TIL) were successfully isolated from 19 solid tumors, yielding an average of 1.3 million TILs per gram of tumor tissue, which can be expanded significantly (30 to 150 times) using rIL-2 in a four-week cultivation process.

The expanded TILs demonstrated a stronger anti-tumor effect against the patient's own tumors compared to other tumors, indicating their potential for personalized cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The antitumor effects of tumor-infiltrating lymphocytes (TIL) being proliferated in vitro]. Zhang, BX.[2016]

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]

Tumor-infiltrating lymphocytes (TILs) and lymphocytes from draining lymph nodes (DLNs) showed better proliferation and longer-lasting growth compared to peripheral blood lymphocytes (PBLs) when cultured with autologous tumor cells, indicating their potential effectiveness in cancer therapy.

Specific lytic activity against autologous tumors was observed in TILs and DLNs from some patients, suggesting that these immune cells can be harnessed for targeted cancer treatment, particularly after prolonged culture and restimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative studies of the long-term growth of lymphocytes from tumor infiltrates, tumor-draining lymph nodes, and peripheral blood by repeated in vitro stimulation with autologous tumor. Skornick, Y., Topalian, S., Rosenberg, SA.[2006]

Tumor-infiltrating lymphocytes (TIL) from human metastatic melanoma were primarily CD8+ T lymphocytes, with 10-20% capable of binding to the patient's own tumor cells, indicating a potential for targeted immune response.

When cultured with recombinant interleukin 2 (rIL-2), these TIL proliferated and differentiated into cytotoxic T lymphocytes (CTL), suggesting they may be immature CTL precursors that can be activated to attack tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tumor-infiltrating lymphocytes from human metastatic melanoma]. Itoh, K.[2006]

LN-145, a tumor-infiltrating lymphocyte therapy, shows promise for patients with non-small cell lung cancer who have not responded to previous treatments, including PD-1 or PD-L1 inhibitors, with an overall response rate of 21.4%.

The median duration of response for LN-145 therapy has not yet been reached after 8.2 months of follow-up, indicating potential long-lasting effects for responders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meaningful Response to TILs in NSCLC. [2022]

In a Phase 2 trial involving 153 patients with advanced melanoma who had previously progressed on immune checkpoint inhibitors, lifileucel showed an objective response rate (ORR) of 31.4%, indicating its potential effectiveness in this challenging patient population.

The treatment demonstrated durable responses, with 41.7% of patients maintaining their response for at least 18 months, and a favorable safety profile, although common severe side effects included thrombocytopenia and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study. Chesney, J., Lewis, KD., Kluger, H., et al.[2023]

A new method for isolating tumor-infiltrating lymphocytes (TIL) that express specific dysfunction markers (CD39, PD-1, and TIGIT) has been developed, allowing for efficient identification of neoantigen-reactive T-cell receptors (TCRs) from resected tumors, which is crucial for creating targeted cancer therapies.

Despite the initial success in isolating TIL with potential neoantigen reactivity, most expanded TIL populations showed functional impairment, indicating that while the isolation method is effective, the in vitro expansion process may hinder the TIL's ability to recognize and attack tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell surface marker-based capture of neoantigen-reactive CD8+ T-cell receptors from metastatic tumor digests. Chatani, PD., Lowery, FJ., Parikh, NB., et al.[2023]

A retrospective analysis of 21 patients with advanced cutaneous melanoma showed that nonselected autologous tumor-infiltrating lymphocytes (TILs) resulted in a high overall response rate of 67% and a complete response rate of 19%, indicating significant efficacy even in patients who had previously undergone PD-1 inhibition.

The treatment was found to be safe, with no treatment-related deaths and a median overall survival of 21.3 months, suggesting that TIL therapy could be a promising option for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical feasibility and treatment outcomes with nonselected autologous tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma. Pillai, M., Jiang, Y., Lorigan, PC., et al.[2022]

In a study of 17 lung adenocarcinoma patients, T lymphocytes were found to be the main component of tumor infiltrating lymphocytes (TIL) in malignant pleural effusions, with T helper cells outnumbering T killer cells.

The study demonstrated that TILs with a high proliferation rate had a significantly greater ability to kill autologous tumor cells (50.51%) compared to those with a low proliferation rate (29.04%), suggesting that TILs from pleural effusions could be effective for cellular immunotherapy against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tumor infiltrating T lymphocyte components in malignant pleural effusion of lung adenocarcinoma and their killing activities to autologous tumor cells]. Xia, Z., Liu, J., Qing, B., et al.[2020]

In a study involving 21 cancer patients, tumor-infiltrating lymphocytes (TIL) were successfully activated with interleukin 2 (IL-2) and showed significant tumor-killing activity, leading to complete regression of malignant pleural effusions in one pancreatic cancer patient and nearly complete regression of malignant ascites in a gastric cancer patient.

The optimal concentration of IL-2 for maximizing TIL proliferation and tumor-killing ability was found to be 1,500 IU/ml, demonstrating that adoptive transfer of activated TIL can be an effective immunotherapy approach in treating certain cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical application of adoptive immunotherapy by cytotoxic T lymphocytes induced from tumor-infiltrating lymphocytes]. Yamaue, H., Tanimura, H., Tsunoda, T., et al.[2011]

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. China pubmed.ncbi.nlm.nih.gov

[The antitumor effects of tumor-infiltrating lymphocytes (TIL) being proliferated in vitro]. [2016]

3. 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]

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

Comparative studies of the long-term growth of lymphocytes from tumor infiltrates, tumor-draining lymph nodes, and peripheral blood by repeated in vitro stimulation with autologous tumor. [2006]

5. Japan pubmed.ncbi.nlm.nih.gov

[Tumor-infiltrating lymphocytes from human metastatic melanoma]. [2006]

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

Meaningful Response to TILs in NSCLC. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study. [2023]

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

Cell surface marker-based capture of neoantigen-reactive CD8+ T-cell receptors from metastatic tumor digests. [2023]

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

Clinical feasibility and treatment outcomes with nonselected autologous tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma. [2022]

10. China pubmed.ncbi.nlm.nih.gov

[Tumor infiltrating T lymphocyte components in malignant pleural effusion of lung adenocarcinoma and their killing activities to autologous tumor cells]. [2020]

11. Japan pubmed.ncbi.nlm.nih.gov

[Clinical application of adoptive immunotherapy by cytotoxic T lymphocytes induced from tumor-infiltrating lymphocytes]. [2011]