Autologous LN-145 for Lung Cancer

Recruiting at 64 trial locations

Overseen By Iovance Biotherapeutics Study Team lungcelltherapy.com

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

170 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, LN-145 (a type of cell therapy using autologous tumor infiltrating lymphocytes), for individuals with metastatic non-small-cell lung cancer (NSCLC) that has spread and did not respond to initial treatments. Researchers aim to evaluate how well LN-145 works in different patient groups, including those with varying levels of a protein called PD-L1 and those who have previously received LN-145. This trial might suit individuals with stage IV NSCLC who have tried chemotherapy and immunotherapy, yet their disease continues to progress. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that LN-145, a type of cell therapy, is generally safe for people. In several studies, patients who received LN-145 did not experience any long-term safety issues, indicating that the treatment did not cause unexpected or serious side effects over time.

Earlier trials showed that side effects can occur but are usually manageable. For example, patients might experience temporary issues like fever or tiredness, which are common with many treatments and typically not severe.

The ongoing studies focus on understanding the treatment's safety and effectiveness, indicating that earlier research has already demonstrated some level of safety.

Overall, LN-145 appears to be a promising option, with researchers and doctors closely monitoring its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about LN-145 for lung cancer because it uses a unique approach called tumor-infiltrating lymphocytes (TIL) therapy. Unlike standard treatments such as chemotherapy or targeted therapies that attack cancer cells directly, LN-145 harnesses the patient's own immune cells to fight the cancer. This personalized method involves harvesting immune cells from the patient's tumor, expanding them in the lab, and then reinfusing them to boost the body's natural cancer-fighting abilities. This approach not only targets hard-to-treat tumors but could also potentially lead to longer-lasting responses by training the immune system to recognize and attack cancer cells more effectively.

What evidence suggests that LN-145 could be an effective treatment for metastatic non-small-cell lung cancer?

Research has shown that LN-145, a treatment using tumor-infiltrating lymphocytes (TILs), might help treat advanced non-small-cell lung cancer (NSCLC). In this trial, participants will receive LN-145, which has shown promise as a one-time treatment for patients with advanced cancer. Specifically, LN-145 has been effective for those with advanced melanoma, particularly patients who did not respond to other treatments. Additionally, early results on the safety and effectiveness of LN-145 for advanced lung cancer are promising. This treatment uses the body's own immune cells to fight cancer, offering a strong option for those whose cancer hasn't responded to other treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Iovance Biotherapeutics Study Team

Principal Investigator

Iovance Biotherapeutics

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• LN-145

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.

How Is the Trial Designed?

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

LN-145 is already approved in United States for the following indications:

Approved in United States as LN-145 for:

• Cervical Cancer
• Metastatic Melanoma
• Head and Neck Squamous Cell Carcinoma (HNSCC)
• Non-Small Cell Lung Cancer (NSCLC)

Who Is Running the Clinical Trial?

Iovance Biotherapeutics, Inc.

Lead Sponsor

Trials

26

Recruited

1,800+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

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]

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38563600/

Lifileucel, an Autologous Tumor-Infiltrating Lymphocyte ... In this phase 2 multicenter study, we evaluated the efficacy and safety of lifileucel (LN-145), an autologous tumor-infiltrating lymphocyte cell ...

2. aacrjournals.org aacrjournals.org/cancerdiscovery/article/14/8/1389/746508/Lifileucel-an-Autologous-Tumor-Infiltrating

Lifileucel, an Autologous Tumor-Infiltrating Lymphocyte ... In this phase 2 trial, the tumor-infiltrating lymphocyte therapy lifileucel showed potential as a one-time treatment option for patients with metastatic.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04614103

Study Details | NCT04614103 | Autologous LN-145 in ... LN-145 is a ready-to-infuse TIL therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI and further optimized by ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00765

Long-Term Efficacy and Safety of Lifileucel Tumor ... Patients with advanced melanoma resistant to immune checkpoint or BRAF/MEK inhibitors have treatment options with relatively low efficacy.

5. jitc.bmj.com jitc.bmj.com/content/9/Suppl_2/A486

LN-145) monotherapy in patients with advanced, immune ... Here, we report the first safety and efficacy data for LN-145 as monotherapy in patients with advanced NSCLC. Methods IOV-COM-202 (NCT03645928) ...

6. med.uc.edu med.uc.edu/institutes/cancer/blog/cancer-research/2023/11/30/clinical-trial-ln-145-nsclc

Clinical Trial Highlight: Phase 2 Study Evaluates LN-145 in ... This clinical trial is designed to study the efficacy of LN-145 on patients with advanced lung cancer.