CD40L-augmented TIL for Melanoma

Overseen By Kim Sprenger

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

Trial Summary

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.

What data supports the effectiveness of the treatment CD40L-augmented TIL for Melanoma?

Research shows that CD40L can boost the immune system's ability to fight cancer by activating T cells (a type of immune cell) and causing cancer cells to die. This suggests that CD40L-augmented TIL could enhance the body's natural defenses against melanoma. ^{1 2 3 4 5}

Is CD40L-augmented TIL therapy safe for humans?

CD40L-based therapies, including those using CD40 agonists, have been tested in early clinical trials and found to be generally safe, with side effects like temporary cytokine release (immune system activation) and manageable liver issues. These treatments have shown potential in cancer therapy, including melanoma, with side effects being mostly mild to moderate and controllable. ^{2 4 5 6 7}

How is CD40L-augmented TIL treatment different from other melanoma treatments?

CD40L-augmented TIL treatment is unique because it enhances the immune response by using CD40L to activate T cells and other immune cells, which can directly attack melanoma cells and stimulate a stronger immune response. This approach differs from traditional treatments by focusing on boosting the body's own immune system to fight the cancer. ^{2 4 5 7 8}

What is the purpose of this trial?

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, cutaneous non-acral melanoma, (n=26); Cohort 2: Mucosal melanoma, uveal melanoma, (n=10)). Patients will undergo an excision of a readily accessible tumor for preparation of TIL. Eligible patients with progressive disease after standard of care therapy will undergo lymphodepletion with cyclophosphamide and fludarabine followed by CD40L-augmented TIL and standard of care bolus dose interleukin-2 (short-course IL-2).

Research Team

Lilit Karapetyan

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy of CD40 Agonists Is Mediated by Distinct cDC Subsets and Subverted by Suppressive Macrophages. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Potent Activation of Human T Cells by mRNA Encoding Constitutively Active CD40. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Stimulation of CD40 on immunogenic human malignant melanomas augments their cytotoxic T lymphocyte-mediated lysis and induces apoptosis. [2017]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

CD40L - a multipotent molecule for tumor therapy. [2019]

5. England pubmed.ncbi.nlm.nih.gov

CD40 expressed on human melanoma cells mediates T cell co-stimulation and tumor cell growth. [2019]

6. Greece pubmed.ncbi.nlm.nih.gov

Characteristics and clinical trial results of agonistic anti-CD40 antibodies in the treatment of malignancies. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

CD40 Agonist Antibodies in Cancer Immunotherapy. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Local irradiation does not enhance the effect of immunostimulatory AdCD40L gene therapy combined with low dose cyclophosphamide in melanoma patients. [2022]