TIL Therapy for Skin Cancer

Overseen By Karam Khaddour, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Karam Khaddour

Must not be taking: Systemic steroids

Disqualifiers: Organ transplant, Brain metastases, 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: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for specific skin cancers, focusing on cutaneous squamous cell carcinoma (CSCC) and Merkel cell carcinoma (MCC). Researchers aim to evaluate the effectiveness of combining tumor-infiltrating lymphocyte (TIL) therapy, chemotherapy, and Interleukin-2 (a protein that boosts the immune system) for patients whose cancer did not respond to previous immunotherapy treatments. Participants must have CSCC or MCC that cannot be surgically removed and has spread or recurred after treatment. Those previously treated with immunotherapy, whose cancer continues to progress, may be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, contributing to significant advancements in cancer therapy.

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

Research has shown that tumor-infiltrating lymphocyte (TIL) therapy, such as LN-145, holds promise for treating various cancers, including skin cancers like cutaneous squamous cell carcinoma (CSCC) and Merkel cell carcinoma (MCC). Studies indicate that patients generally tolerate TIL therapy well. Common side effects include tiredness, fever, and low blood cell counts, but these are mostly manageable.

Chemotherapy drugs like Fludarabine and Cyclophosphamide, often used in cancer treatments, can cause side effects such as nausea and a weakened immune system. Patients typically manage these side effects with supportive care.

Interleukin-2 (IL-2), another component of the treatment, can cause flu-like symptoms, but most patients tolerate it with proper medical support.

Overall, despite some side effects, the treatments are considered safe for use in current clinical studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about LN-145 for skin cancer because it uses a unique approach called Tumor-Infiltrating Lymphocyte (TIL) therapy. Unlike standard treatments such as surgery, radiation, or chemotherapy, which work by removing or killing cancer cells directly, LN-145 harnesses a patient's own immune cells to attack the cancer. This personalized treatment involves collecting immune cells from the patient's tumor, expanding them in the lab, and then infusing them back into the patient to target and destroy cancer cells more effectively. This method holds promise for being more precise and potentially more effective, especially for tough-to-treat skin cancers like cutaneous squamous cell carcinoma (CSCC) and Merkel cell carcinoma (MCC).

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

Research has shown that tumor-infiltrating lymphocyte (TIL) therapy, such as LN-145, could be effective for certain cancers, including melanoma and other solid tumors. Studies have found that TIL therapy can often reduce tumor size. In this trial, participants with skin cancer will receive TIL therapy. Specifically, Cohort A will focus on cutaneous squamous cell carcinoma (CSCC), where TIL therapy might work well by using the body's own immune cells to fight the cancer. Cohort B will focus on Merkel Cell Carcinoma (MCC), where TIL therapy may help by increasing the number of cancer-fighting immune cells in the tumors. Early evidence suggests that these treatments could offer new hope for patients who haven't had success with other therapies. ^{1 2 6 7 8}

Who Is on the Research Team?

Karam Khaddour, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with Cutaneous squamous cell carcinoma (CSCC) or Merkel Cell Carcinoma (MCC) who have previously undergone immunotherapy. Participants should meet specific health criteria to be eligible.

Inclusion Criteria

My cancer is confirmed as CSCC or MCC, including mixed types or sun-induced.

Provide written informed consent, including understanding the need for intensive supportive care measures and willingness to undergo such measures, and written authorization for use and disclosure of protected health information

I am 18 years old or older.

Exclusion Criteria

Pregnant or breastfeeding

I have not had another type of cancer in the last year, except for certain exceptions.

I do not have any illnesses that would make this study unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

TIL Harvest and Baseline

Surgical procedure to collect tissue for TIL harvest and baseline assessments

1 week

1 visit (in-person)

Lymphodepleting Chemotherapy

Participants receive Fludarabine and Cyclophosphamide to prepare for TIL infusion

5 days

Daily visits (in-person)

TIL Infusion and IL-2 Administration

TIL infusion followed by IL-2 administration for up to 6 doses

2 weeks

Daily visits (in-person)

Initial Follow-up

Imaging and assessments at weeks 6 and 12 post-treatment

12 weeks

2 visits (in-person)

Long-term Follow-up

Participants are monitored every 3 months for up to 3 years for safety and effectiveness

3 years

Quarterly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Interleukin-2
• LN-145

Trial Overview

The study tests the combination of TIL therapy (LN-145), standard chemotherapy drugs Fludarabine and Cyclophosphamide, and Interleukin-2. It aims to assess the safety and effectiveness of this treatment regimen in affected patients.

How Is the Trial Designed?

Group I: Cohort B: MCC Autologous TIL Therapy Experimental Treatment 4 Interventions

4 participants with MCC will complete: * Screening visit * Surgical procedure to collect tissue, called TIL harvest * Baseline visit * Days -5 through -1: Predetermined dose of Lymphodepleting Chemotherapy, Fludarabine, 1x daily * Days -5 and -4: Predetermined dose of Lymphodepleting Chemotherapy, Cyclophosphamide, 1x daily * Day 0: TILs infusion * Days 0, 1, 2, 3, 4, and 14: Predetermined dose of IL-2 1x daily for up to 6 doses * Imaging at weeks 6 and 12 * End of treatment visit with imaging * Long term follow up every 3 months for up to 3 years

Group II: Cohort A: CSCC Autologous TIL Therapy Experimental Treatment 4 Interventions

10 participants with CSCC will complete: * Screening visit * Surgical procedure to collect tissue, called TIL harvest * Baseline visit * Days -5 through -1: Predetermined dose of Lymphodepleting Chemotherapy, Fludarabine, 1x daily * Days -5 and -4: Predetermined dose of Lymphodepleting Chemotherapy, Cyclophosphamide, 1x daily * Day 0: TIL infusion * Days 0, 1, 2, 3, 4, and 14: Predetermined dose of IL-2 1x daily for up to 6 doses * Imaging at weeks 6 and 12 * End of treatment visit with imaging * Long term follow up every 3 months for up to 3 years

Who Is Running the Clinical Trial?

Karam Khaddour

Lead Sponsor

Iovance Biotherapeutics, Inc.

Industry Sponsor

Trials

26

Recruited

1,800+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07288073

NCT07288073 | TIL Therapy in cSCC and MCC

The purpose of this research study is to test the safety and effectiveness of a tumor-infiltrating lymphocyte (TIL) cellular therapy, ...

2.

smartpatients.com

smartpatients.com/trials/NCT07288073

TIL Therapy in cSCC and MCC

The purpose of this research study is to test the safety and effectiveness of a tumor-infiltrating lymphocyte (TIL) cellular therapy, ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12382571/

Efficacy and safety of one-time autologous tumor-infiltrating ...

Data suggest that TIL cell therapy may be a potential treatment option for patients with recurrent and/or metastatic HNSCC and support further ...

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1040842825000599

Outcomes of tumor-infiltrating lymphocyte therapy in solid ...

TIL therapy is effective in treating solid tumors, especially melanoma, but its results vary according to the kind of cancer as well as tumour ...

5.

targetedonc.com

targetedonc.com/view/autologous-til-cell-therapy-a-potential-next-line-of-treatment-for-hnscc

Autologous TIL Cell Therapy: A Potential Next Line of ...

The study highlighted the feasibility of generating TILs for HNSCC, despite 98% of patients experiencing treatment-emergent adverse events.

6.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.TPS6096

A phase 2, multicenter study to evaluate the efficacy and ...

A phase 2, multicenter study to evaluate the efficacy and safety of autologous tumor infiltrating lymphocytes (LN-145) for the treatment of ...

7.

onclive.com

onclive.com/view/immunotherapy-treatment-options-in-high-risk-or-locally-advanced-metastatic-non-melanoma-and-melanoma-an-evolving-treatment-landscape

Immunotherapy Treatment Options in High-Risk or Locally ...

Cemiplimab and pembrolizumab studies show promise in treating high-risk CSCC, with neoadjuvant therapies potentially reducing surgical needs ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03108495

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.