TIL Therapy for Cancer

AA
Overseen ByAmir A Jazaeri
Age: Any Age
Sex: Any
Trial Phase: Phase 2
Sponsor: M.D. Anderson Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies new treatments for certain types of cancer, including ovarian cancer, triple-negative breast cancer, anaplastic thyroid cancer, and specific bone and soft tissue sarcomas. Researchers are testing whether special white blood cells, taken from a patient's tumor, can effectively target and destroy cancer cells. Participants might receive different versions of these cell treatments, known as Autologous Tumor Infiltrating Lymphocytes LN-145. This trial may suit individuals whose cancer has not responded to treatment or has returned, and who have a tumor that can be biopsied for cell collection. As a Phase 2 trial, this research focuses on measuring how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that any prior therapy directed at the malignant tumor, including radiation therapy, chemotherapy, and biologic/targeted agents, must be stopped at least 28 days before enrollment. However, palliative therapy may be allowed during the screening period with approval from the principal investigator.

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

Research has shown that treatments using a patient's own immune cells, known as tumor infiltrating lymphocytes (TILs), such as LN-145 and LN-145-S1, have been studied in various cancers. These treatments involve extracting T-cells from a patient’s tumor, cultivating them in a lab, and then reintroducing them to the patient to combat the cancer.

For LN-145, studies have found it to be generally well-tolerated. Specifically, in patients with cervical cancer, the treatment demonstrated an acceptable safety profile, meaning it did not cause severe unexpected side effects. Similarly, research with head and neck cancer patients found that combining LN-145 with pembrolizumab was safe and showed promising results.

Regarding LN-145-S1, studies also suggest it is safe to use. One study indicated that this treatment could be a potential option for head and neck cancer, with safety data supporting further research.

It is important to note that while these treatments show promise, they remain under study. They are not yet approved for all conditions, and the full range of possible side effects is still being understood.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they harness the power of the body's own immune cells, specifically tumor-infiltrating lymphocytes (TILs), to fight cancer. Unlike traditional treatments like chemotherapy and radiation, which target cancer cells broadly, TIL therapy involves using a patient's own immune cells, which are grown and activated outside the body before being reintroduced to target cancer more precisely. Additionally, the combination of TILs with immune checkpoint inhibitors like nivolumab and ipilimumab provides a two-pronged attack, potentially enhancing the immune response against tumors. This unique approach offers hope for patients with hard-to-treat cancers, like ovarian cancer, sarcomas, triple negative breast cancer, and thyroid cancer, by targeting cancer cells in a highly personalized way.

What evidence suggests that this trial's treatments could be effective for cancer?

Research shows that certain immune cells, called tumor-infiltrating lymphocytes (TILs), can effectively attack and destroy cancer cells, especially in patients with solid tumors like melanoma. This trial studies LN-145 and LN-145-S1 treatments. LN-145, used in the thyroid cohort, involves TILs taken from a patient's tumor and grown in a lab. Studies have shown promising results with LN-145, where 66% of patients experienced a complete response, meaning their cancer disappeared. LN-145-S1, part of the treatment for ovarian cancer, sarcomas, and triple-negative breast cancer, uses a special method to select specific T-cells, aiming to enhance effectiveness. Early findings suggest these treatments could help patients with ovarian cancer, triple-negative breast cancer, anaplastic thyroid cancer, and certain sarcomas that have not responded to other treatments.16789

Who Is on the Research Team?

Amir Anthony Jazaeri | MD Anderson ...

Amir A. Jazaeri

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with specific types of cancer (ovarian, TNBC, thyroid, osteosarcoma or other bone/soft tissue sarcomas) that are resistant to treatment or have returned. Participants must have a tumor suitable for biopsy and meet certain health criteria like heart and lung function tests. They should not be HIV positive or have uncontrolled illnesses.

Inclusion Criteria

I can have a piece of my tumor removed for testing, separate from the main cancer area.
I stopped any cancer treatments 28 days before enrolling for TIL therapy, except with PI approval for palliative care.
My heart test (stress echo) results were normal, or I had an alternative heart check approved by a cardiologist.
See 9 more

Exclusion Criteria

I do not have severe ongoing side effects from previous treatments, active hepatitis, heart issues, or a history of certain cell therapies.
I had severe diarrhea or colitis from past immunotherapy but have been symptom-free for 6 months or had a normal colonoscopy.
I do not have any severe ongoing illnesses that are not under control.
See 1 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive cyclophosphamide, fludarabine, LN-145 or LN-145-S1, and aldesleukin. For some cohorts, nivolumab and ipilimumab are also administered.

Approximately 1-2 weeks
Multiple visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at 18 weeks, 6, 9, 12, 18, and 24 months, then every 3 months for at least 3 years.

Up to 3 years
Regular follow-up visits

Extension

Participants may continue to receive nivolumab every 4 weeks in the absence of disease progression or unacceptable toxicity.

Up to 12 weeks post-treatment

What Are the Treatments Tested in This Trial?

Interventions

  • Autologous Tumor Infiltrating Lymphocytes LN-145
  • Autologous Tumor Infiltrating Lymphocytes LN-145-S1
Trial Overview The trial is testing LN-145 and LN-145-S1, which are therapies using the patient's own T-cells grown from their tumors to fight cancer. It examines how well these cells can target and destroy cancer cells in patients who haven't responded to standard treatments.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Thyroid Cohort (LN-145)Experimental Treatment6 Interventions
Group II: ICI Ovarian Cancer, Sarcomas, Triple Negative Breast Cancer (LN-145-S1, nivolumab)Experimental Treatment9 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

Iovance Biotherapeutics, Inc.

Industry Sponsor

Trials
26
Recruited
1,800+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

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.
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) 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.
[The antitumor effects of tumor-infiltrating lymphocytes (TIL) being proliferated in vitro].Zhang, BX.[2016]
Tumor-infiltrating lymphocytes (TILs) are a promising treatment for solid tumors, as they are derived from the patient's own body and have fewer adverse reactions compared to genetically modified therapies.
Despite their potential, the effectiveness of TIL therapy is currently limited by challenges in the immune microenvironment and antigen mutations, which the article reviews in terms of enhancing their therapeutic impact.
Tumor-infiltrating lymphocytes: Warriors fight against tumors powerfully.Lin, B., Du, L., Li, H., et al.[2021]

Citations

NCT03449108 | LN-145 or LN-145-S1 in Treating Patients ...This phase II trial studies how well autologous tumor infiltrating lymphocytes LN-145 (LN-145) or LN-145-S1 works in treating patients with ovarian cancer ...
Research progress of immunotherapy against anaplastic ...The results demonstrated that 66% of the patients had a full response, 16% had stable illness, and 16% had progressing disease. The median ...
NCT03108495 | Study of LN-145, Autologous Tumor ...After reviewing available safety and efficacy data to date, Iovance concluded the study reached the required number of events for evaluation of study endpoints.
Efficacy and safety of one-time autologous tumor-infiltrating ...Results from this study suggest TIL cell therapy may serve as a potential treatment option for patients with HNSCC and support further ...
Clinical Study to Assess Efficacy and Safety of LN-145 ...This phase II trial studies how well autologous tumor infiltrating lymphocytes LN-145 (LN-145) or LN-145-S1 works in treating patients with ovarian cancer.
Safety and efficacy of adoptive cell transfer using ...LN-145 results in 44% ORR in previously treated cervical cancer patients with acceptable safety and efficacy profile.
LN-145) in combination with pembrolizumab for advanced, ...Adoptive cell therapy utilizing tumor infiltrating lymphocytes (TIL; LN-145) leverages and enhances the body's natural defense against cancer. • ...
8.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/40854613/
Efficacy and safety of one-time autologous tumor-infiltrating ...Results from this study suggest TIL cell therapy may serve as a potential treatment option for patients with HNSCC and support further ...
353 Safety and efficacy of tumor infiltrating lymphocytes ...LN-145 can be safely combined with pembrolizumab in patients with metastatic HNSCC. LN-145 plus pembrolizumab shows early signs of improved efficacy.
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