CD40L-augmented TIL for Melanoma

Overseen By Tina Swartzlander

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Systemic steroids, Immunosuppressives

Disqualifiers: Ischemic heart disease, Immunodeficiency, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CD40L-augmented TIL, a type of cell therapy, for individuals with advanced melanoma, a type of skin cancer. The researchers aim to determine if this treatment is safe and effective for patients whose cancer hasn't responded to standard therapies. Participants will have a tumor removed to prepare the treatment and will receive additional medications to aid the process. This trial suits those with advanced melanoma that has not improved with usual treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain medications, such as systemic steroid therapy above a low dose, at least one week before starting the trial. If you are on immunosuppressive medications or high-dose steroids, you may need to taper off before participating.

Is there any evidence suggesting that CD40L-augmented TIL is likely to be safe for humans?

Research shows that Tumor-Infiltrating Lymphocyte (TIL) therapy has received FDA approval for treating melanoma, indicating its safety for this condition is well-understood. Studies are ongoing to test a new version called CD40L-augmented TIL, focusing on its safety.

Early results from other studies examine how well patients tolerate CD40L-augmented TIL, assessing how patients handle the treatment. Researchers closely monitor safety, especially after every four patients, to detect any harmful effects early.

While detailed safety information for CD40L-augmented TIL is still being collected, its similarity to the approved TIL therapy suggests it might be safe for treating melanoma. However, this treatment remains experimental, and further research is needed to confirm its safety. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for melanoma?

Researchers are excited about CD40L-augmented TIL for melanoma because it introduces a novel approach to cancer treatment by enhancing the activity of tumor-infiltrating lymphocytes (TILs) with the CD40 ligand (CD40L). Most traditional treatments for melanoma, like immune checkpoint inhibitors and targeted therapies, focus on blocking cancer growth or boosting the immune response in a broader way. However, CD40L-augmented TIL specifically supercharges the immune cells already present in the tumor, potentially increasing their ability to attack cancer cells more effectively. This targeted enhancement could lead to better outcomes, especially for patients with rare melanoma subtypes, where existing treatments are limited.

What evidence suggests that CD40L-augmented TIL might be an effective treatment for melanoma?

Research has shown that a new treatment using enhanced immune cells, called CD40L-augmented tumor-infiltrating lymphocytes (TIL), may help treat advanced melanoma. CD40L activates immune cells like B-cells, potentially boosting the body's ability to fight cancer. This trial will evaluate CD40L-augmented TIL in different cohorts, including a Phase I safety trial, a Phase II efficacy trial, and a cohort for rare melanoma subtypes. Early results suggest these modified TILs could help melanoma patients who haven't responded to other treatments. While more clinical data is needed, this therapy offers a promising new way to address melanoma. ^{1 2 6 7 8}

Who Is on the Research Team?

Lilit Karapetyan, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with advanced melanoma, specifically cutaneous acral and non-acral melanoma (26 people), as well as mucosal and uveal melanoma (10 people). Participants must have progressive disease after standard treatments. They will undergo tumor removal for TIL preparation and must be fit for lymphodepletion.

Inclusion Criteria

Participants must be seronegative for HIV, hepatitis B, and hepatitis C

Participants must be willing to sign an informed consent document

My melanoma is advanced and cannot be removed by surgery.

Exclusion Criteria

Participants with primary or acquired immunodeficiency disorders

Pregnant or breastfeeding women

Participants with severe hypersensitivity reactions to study agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Tumor Excision

Patients undergo an excision of a readily accessible tumor for preparation of TIL

1 week

Lymphodepletion

Eligible patients undergo lymphodepletion with cyclophosphamide and fludarabine

1 week

Treatment

Patients receive a single dose of CD40L-augmented TIL followed by standard of care bolus dose interleukin-2

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Participants are monitored for long-term outcomes such as overall survival and progression-free survival

Up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

• CD40L-augmented TIL

Trial Overview

The study tests a single dose of CD40L-augmented TIL in two cohorts of melanoma patients. It involves removing a tumor to prepare the TIL, then treating patients with cyclophosphamide and fludarabine to weaken their immune system before administering the TIL followed by interleukin-2.

How Is the Trial Designed?

Group I: Cohort 2: Rare melanoma subtypes Experimental Treatment 4 Interventions

Cohort 2 will include n=10 patients with the rare melanoma histological subtypes of mucosal or uveal melanoma and will be used to assess feasibility and toxicity of the treatment in those rare melanoma subtypes.

Group II: Cohort 1: Phase II efficacy trial Experimental Treatment 4 Interventions

If there are 2 responders or more, the trial will continue to enroll additional 14 patients in the 2nd stage.

Group III: Cohort 1: Phase I safety trial Experimental Treatment 4 Interventions

Participants will receive a single dose of CD40L-Augmented TIL. Toxicity will be evaluated at every 4 patients. The study may enroll 16-20 patients to reach 12 TIL safety evaluable patients.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Published Research Related to This Trial

CD40 agonists have shown potential in cancer immunotherapy, demonstrating moderate antitumor effects in some tumors, based on early clinical trials.

The adverse events associated with CD40 agonists, such as cytokine release and hepatotoxicity, have been mostly transient and manageable, suggesting a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and clinical trial results of agonistic anti-CD40 antibodies in the treatment of malignancies. Li, DK., Wang, W.[2020]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06961357

NCT06961357 | Clinical Trial of CD40L-augmented TIL for ...

This is a phase I/II clinical trial of a single dose of CD40L-augmented TIL administered in patients with advanced melanoma (Cohort 1: Cutaneous acral ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666636724007838

Tumor-Infiltrating Lymphocyte Therapy: A New Frontier

The goal of knocking out PDCD-1 in TILs is to enhance TIL efficacy and potentially avoid the need for systemic anti-PD-1 therapy and its associated toxicities.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11979601/

CD40L stimulates tumor-infiltrating B-cells and improves ex ...

We now report the results obtained in human melanoma and lung TIL of CD40L-enhanced TIL expansion and quality and provide mechanistic insight ...

4.

cancer.gov

cancer.gov/research/participate/clinical-trials/intervention/cd40l-augmented-autologous-tumor-infiltrating-lymphocytes

Clinical Trials Using CD40L-augmented Autologous Tumor ...

Review the clinical trials studying cd40l-augmented autologous tumor infiltrating lymphocytes on this list and use the filters to refine the results by age ...

5.

melanoma.org

melanoma.org/news-press/research-creates-hope-and-hope-changes-everything/

Research Creates Hope and Hope Changes Everything

Dr. Karapetyan's project is timely as the first cancer tumor infiltrating lymphocyte (TIL) therapy (AMTAGVI™) was recently approved by the FDA ...

6.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-05811

Lymphodepletion Chemotherapy, CD40L-Augmented ...

To evaluate the safety and toxicity of CD40L-augmented TIL administered in patients with advanced melanoma. II. To evaluate the efficacy of CD40L-augmented ...

7.

moffitt.org

moffitt.org/cancers/melanoma/clinical-trials/

Melanoma Clinical Trials

Phase I/II Clinical Trial of CD40L-augmented Tumor Infiltrating Lymphocytes (TIL) for Patients with Advanced Melanoma Condition: Cutaneous Intervention ...

8.

withpower.com

withpower.com/clinical-trials/for-uveal-melanoma?page=2

Top Uveal Melanoma Clinical Trials | Power

This is a phase I/II clinical trial of a single dose of CD40L-augmented TIL administered in patients with advanced melanoma (Cohort 1: Cutaneous acral melanoma, ...