What is the mechanism of action of this treatment?

Common cancer treatments, particularly immunotherapies like LN-145 or LN-145-S1, work by harnessing the patient's immune system to target and destroy cancer cells. These therapies involve collecting and modifying the patient's T-cells to enhance their ability to recognize and kill tumor cells. This personalized approach is crucial for cancer patients as it offers a targeted treatment option that can be more effective and potentially less harmful than traditional therapies, especially for those with cancers that have relapsed or are resistant to other treatments.

What side effects are associated with this type of intervention?

Common side effects of cancer treatments, particularly those involving autologous T-cell therapies like LN-145 or LN-145-S1, include cytokine release syndrome (CRS), which can cause fever, fatigue, and low blood pressure. Neurotoxicity is another potential side effect, leading to confusion, headaches, or seizures. Radiotherapy, often combined with immunotherapy, can cause skin irritation, fatigue, and localized pain. Chemotherapy, another common treatment, typically results in nausea, hair loss, and increased susceptibility to infections. Targeted therapies may cause side effects such as hypertension, diarrhea, and liver dysfunction. Each treatment's side effects vary based on the specific drugs and protocols used.

What prior FDA approvals exist?

The FDA has approved several therapies that involve autologous T-cells targeting and killing tumor cells, similar to LN-145 and LN-145-S1. Notably, CAR-T cell therapies such as lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel have been approved for the treatment of relapsed or refractory large B-cell lymphoma. These therapies involve modifying a patient's T-cells to express a chimeric antigen receptor (CAR) that specifically targets cancer cells, leading to their destruction. These approvals highlight the growing role of personalized immunotherapies in cancer treatment.

What other types of research exist?

Promising novel alternatives to LN-145 or LN-145-S1 for cancer patients include: <ol> <li>CMC-544 (inotuzumab ozogamicin) combined with rituximab for B-cell non-Hodgkin's lymphoma, targeting CD22 and CD20 antigens.</li> <li></li> </ol> Regorafenib, a multitargeted kinase inhibitor, for advanced osteosarcoma. 3. Atezolizumab or durvalumab combined with platinum-etoposide for extensive-stage small cell lung cancer (ES-SCLC). 4. BL22, a recombinant anti-CD22 immunotoxin, for chemotherapy-resistant hairy cell leukemia. 5. LCL-161 combined with rituximab, gemcitabine, and vinorelbine (RGV) for rituximab-resistant B-cell lymphoma.

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CAR T-cell Therapy

TIL Therapy for Cancer

Phase 2

Waitlist Available

Led By Amir A Jazaeri

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects must have an area of tumor amenable to excisional biopsy (core biopsies may be allowed as detailed in protocol) for the generation of TIL separate from, and in addition to, a target lesion to be used for response assessment

Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1

Must not have

Various medical history and conditions including active viral hepatitis, left ventricular ejection fraction (LVEF) < 45%, history of prior adoptive cell therapies, persistent prior therapy-related toxicities greater than grade 2, and others

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a treatment using a patient's own immune cells to fight various cancers that haven't responded to other treatments or have come back. The immune cells are taken from the tumor, grown in a lab, and then reintroduced into the body to target and kill cancer cells. The study aims to see how well this approach works and how safe it is.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include reactions related to immune system activation such as inflammation in various organs, fatigue, digestive issues due to therapy-related toxicity greater than grade 2 if previously experienced with immunotherapy.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can have a piece of my tumor removed for testing, separate from the main cancer area.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I do not have HIV.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have severe ongoing side effects from previous treatments, active hepatitis, heart issues, or a history of certain cell therapies.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective response rate

Secondary study objectives

Overall survival

Progression free survival

Other study objectives

Duration of TIL persistence

Health Related Quality of Life

Immunological phenotype of LN-145 by multichannel flow cytometry

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Thyroid Cohort (LN-145)Experimental Treatment6 Interventions

Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, autologous tumor infiltrating lymphocytes LN-145 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses.

Group II: ICI Ovarian Cancer, Sarcomas, Triple Negative Breast Cancer (LN-145-S1, nivolumab)Experimental Treatment9 Interventions

Ipilimumab will be administered as a single dose prior to tumor resection. Nivolumab will be administered once prior to tumor resection. Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, LN-145-S1 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses. Within 12 weeks after receiving LN-145-S1, patients receive nivolumab IV over 30 minutes every 4 weeks in the absence of disease progression or unacceptable toxicity. The second dose will be administered prior to TIL administration and dosing will continue every 4 weeks and continued until unacceptable toxicity, progression, or start of another cancer therapy.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

2010

Completed Phase 4

~2310

Ipilimumab

2015

Completed Phase 3

~3420

Nivolumab

2015

Completed Phase 3

~4010

Aldesleukin

2012

Completed Phase 4

~1610

Fludarabine

2012

Completed Phase 4

~1860

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common cancer treatments, particularly immunotherapies like LN-145 or LN-145-S1, work by harnessing the patient's immune system to target and destroy cancer cells. These therapies involve collecting and modifying the patient's T-cells to enhance their ability to recognize and kill tumor cells. This personalized approach is crucial for cancer patients as it offers a targeted treatment option that can be more effective and potentially less harmful than traditional therapies, especially for those with cancers that have relapsed or are resistant to other treatments.