Vemurafenib + ACT + IL-2 for Melanoma

Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
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 explores the effects of a new combination treatment for melanoma, a type of skin cancer. The treatment involves vemurafenib, a drug, combined with a special immune cell therapy called Adoptive Cell Therapy (ACT). The focus is on individuals with advanced melanoma that cannot be surgically removed and has specific genetic mutations (B-RAF V600E, D, or K). Participants should have ongoing melanoma despite previous surgeries and may have up to three small untreated brain metastases. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic immunosuppressive steroids or medications for autoimmune diseases, you may not be eligible to participate.

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

Research shows that the combination of vemurafenib, ACT with TIL infusion, and high-dose interleukin-2 (IL-2) is generally safe for people. Each component of this treatment has undergone safety studies in humans.

Vemurafenib has proven effective and safe for patients with advanced skin cancer (metastatic melanoma), with no new safety issues over long-term use. One study showed it remained safe for a large group of patients over two years.

ACT with TIL infusion has been reviewed and found to have manageable side effects for patients with advanced melanoma. A review of several studies found it safe when used with high-dose IL-2.

High-dose IL-2 has shown safety for carefully chosen melanoma patients, even those with cancer spread to the brain. It can be used safely if other treatments do not work.

Overall, research suggests that this combination treatment should be well-tolerated in humans. However, individual responses can vary, so discussing potential risks with healthcare providers is important.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination therapy of vemurafenib, ACT with TIL infusion, and IL-2 for melanoma because it represents a powerful integration of targeted therapy and immunotherapy. Unlike standard treatments such as single-agent chemotherapy or immune checkpoint inhibitors like pembrolizumab, this regimen uses vemurafenib to target the specific BRAF mutation found in many melanoma patients, which can help shrink tumors. Additionally, the use of Tumor Infiltrating Lymphocytes (TIL) in Adoptive Cell Therapy enhances the body's immune response by expanding the patient's own immune cells to attack cancer more effectively. Finally, high-dose IL-2 boosts the immune system, enhancing the effectiveness of the treatment. This multi-faceted approach offers a promising new avenue for patients who may not respond to existing therapies.

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

Research shows that vemurafenib can extend the lives of melanoma patients with the BRAF V600E mutation. It controls the disease in 79% of patients and reduces tumors in more than half of those treated. In this trial, participants will receive a combination therapy that includes vemurafenib, lymphodepletion, ACT (Adoptive Cell Therapy) using TIL (Tumor Infiltrating Lymphocytes), and high-dose interleukin-2 (IL-2). Studies have shown that ACT is effective for melanoma, with up to 50% of patients responding well. High-dose IL-2 has been used for advanced melanoma, with some patients experiencing positive results and even complete tumor disappearance. These treatments work together to enhance the body's immune system to fight melanoma more effectively. Overall, they aim to improve outcomes for patients with advanced melanoma.56789

Who Is on the Research Team?

AS

Amod Sarnaik, M.D.

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Are You a Good Fit for This Trial?

This trial is for adults with stage III or IV melanoma that can't be removed by surgery. They should have good physical health, a specific type of mutation in their cancer (B-RAF V600), and no serious heart rhythm problems. Pregnant women, those with significant psychiatric illness, certain brain metastases, previous BRAF inhibitor treatment, or active infections are excluded.

Inclusion Criteria

I tested positive for Epstein-Barr Virus antibodies.
My largest cancer lesion is bigger than 1 cm or I have more than 3 lesions, but my brain scans show no worsening after treatment.
I am a woman who can have children and have a negative pregnancy test.
See 12 more

Exclusion Criteria

I have not had cancer other than melanoma in the last 2 years.
I have up to 3 untreated brain tumors, with at least one larger than 1 cm or causing swelling.
I do not have any active infections needing IV antibiotics or major illnesses affecting my heart, lungs, or immune system.
See 13 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vemurafenib for about three weeks while T-cells are being grown in the lab, followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2

3 weeks for initial vemurafenib, followed by additional treatment phases

Follow-up

Participants are monitored for safety and effectiveness after treatment, with evaluations at month 12

12 months

Extension

Participants may continue vemurafenib treatment for up to two years

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

  • ACT with TIL Infusion
  • High Dose Interleukin-2 (IL-2)
  • Lymphodepletion
  • Vemurafenib
Trial Overview The study tests a combination therapy for advanced melanoma involving lymphodepletion (weakening the immune system), T-cell infusion (ACT with TIL), high-dose IL-2 to boost immunity, and Vemurafenib targeting cancer cells. It aims to see how well these treatments work together.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Combination TherapyExperimental Treatment4 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials
576
Recruited
145,000+

Citations

Immune correlates and mechanisms of TIL therapy efficacyTIL–ACT has shown significant efficacy in treating melanoma, with a meta-analysis of 13 studies showing response rates of 34% in patients with ...
Complete metabolic response as early predictor of long-term ...Recently, adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) showed superior progression-free survival (PFS) compared with ...
Efficacy of TIL therapy in advanced cutaneous melanoma ...Our data reinforce the evidence that TIL-ACT should be considered as a treatment of choice in second line for metastatic melanoma patients ...
Achievements and challenges of adoptive T cell therapy with ...TIL-based ACT has so far only been tested in smaller phase I/II studies, but these studies consistently confirm an impressive clinical response rate of up to 50 ...
Adoptive Cell Therapy for Solid Tumors: Current Status in ...This study treated 56 heavily pretreated patients with solid tumors, including 4 with immunotherapy-refractory melanoma, with an ORR of 34.8% ( ...
Review Safety of adoptive therapy with tumor-infiltrating ...This meta-analysis examined the safety of TIL-ACT therapy along with HD-IL-2, in advanced melanoma patients. · TIL-ACT presents a safe and manageable toxicity ...
Safety of adoptive therapy with tumor-infiltrating ...This meta-analysis examined the safety of TIL-ACT therapy along with HD-IL-2, in advanced melanoma patients. •. TIL-ACT presents a safe and ...
Tumor-Infiltrating Lymphocyte Therapy for the Treatment of ...Data presented for the first ten infused patients showed promising efficacy (ORR 44.4%, including two complete responses) in ICI-refractory ...
Safety and efficacy of combined treatment with tumor- ...According to computed tomography (CT), the objective response rate is 11.7% (2/17) and disease control is observed in 35% (6/17), including a ...
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