170 Participants Needed

TIL + Pembrolizumab for Melanoma

Recruiting at 1 trial location
Fm
NB
Overseen ByNCI/Surgery Branch Recruitment Center
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

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients must have completed any prior systemic therapy at the time of enrollment, which might imply stopping certain treatments. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment TIL + Pembrolizumab for Melanoma?

Research shows that tumor-infiltrating lymphocytes (TILs) and pembrolizumab, a drug that blocks a protein called PD-1, can help the immune system fight cancer. While studies specifically on melanoma are limited, similar treatments have shown promise in other cancers, suggesting potential benefits for melanoma as well.12345

Is the combination of TIL and Pembrolizumab safe for humans?

Pembrolizumab, also known as KEYTRUDA, has been shown to have a generally acceptable safety profile in various studies, including those for melanoma and multiple myeloma. Some side effects have been reported, such as diarrhea and lung inflammation, but they were manageable and resolved without lasting effects.34678

How is the TIL + Pembrolizumab treatment for melanoma different from other treatments?

The TIL + Pembrolizumab treatment is unique because it combines tumor-infiltrating lymphocytes (TIL), which are immune cells extracted from the patient's own tumor, with pembrolizumab, a drug that helps the immune system attack cancer cells. This combination aims to enhance the body's immune response against melanoma, offering a novel approach compared to standard treatments that typically involve only drugs like pembrolizumab.478910

What is the purpose of this trial?

Background:Cell therapy is an experimental cancer therapy. It takes young tumor infiltrating lymphocytes (Young TIL) cells from a person s tumors and grows them in a lab. Then they are returned to the person. Researchers think adding the drug pembrolizumab might make the therapy more effective.Objective:To test if adding pembrolizumab to cell therapy is safe and effective to shrink melanoma tumors.Eligibility:People ages 18-72 years with metastatic melanoma OF THE SKINDesign:Participants will be screened with:Physical examCT, MRI, or PET scansX-raysHeart and lung function tests if indicatedBlood and urine testsBefore treatment, participants will have:A piece of tumor taken from a biopsy or during surgery in order to grow TIL cellsLeukapheresis: Blood flows through a needle in one arm and into a machine that removes white blood cells.The rest of the blood returns through a needle in the other arm.An IV catheter placed in the chest for getting TIL cells, aldesleukin, and pembrolizumab (if assigned)Participants will stay in the hospital for treatment. This includes:Daily chemotherapy for 1 weekFor some participants, pembrolizumab infusion 1 day after chemotherapyTIL cell infusion 2-4 days after chemotherapy, then aldesleukin infusion every 8 hours for up to 12 dosesFilgrastim injections to help restore your blood countsRecovery for 1-3 weeksAfter treatment, participants will:Take an antibiotic and an antiviral for at least 6 months, as applicableIf assigned, have pembrolizumab treatment every 3 weeks for 3 more doses. They may have another round.Have 2-day follow-up visits every 1-3 months for 1 year and then every 6 months

Research Team

SL

Stephanie L Goff, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults aged 18-70 with metastatic melanoma of the skin, who have had at least one prior treatment. Eligible participants may have up to three small, stable brain tumors and must practice birth control. Excluded are those with severe allergies, immune deficiencies, active infections or major illnesses, pregnant or breastfeeding women, and anyone on systemic steroids.

Inclusion Criteria

Measurable metastatic melanoma with at least one lesion that is resectable for TIL generation
Confirmation of diagnosis of metastatic melanoma by the Laboratory of Pathology of NCI
Patients must have received at least one prior therapy for metastatic melanoma
See 17 more

Exclusion Criteria

Patients who are receiving any other investigational agents
Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant
Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease)
See 9 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
Multiple visits for physical exams, imaging, and lab tests

Treatment

Participants receive a non-myeloablative lymphodepleting regimen, TIL infusion, and high-dose IL-2. Some participants also receive pembrolizumab.

4-6 weeks
Inpatient stay for chemotherapy, TIL infusion, and IL-2 administration

Recovery

Participants recover from treatment and receive supportive care including filgrastim injections.

1-3 weeks
Inpatient stay for recovery and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, with pembrolizumab administered every 3 weeks for 3 more doses if applicable.

1 year
2-day follow-up visits every 1-3 months

Long-term Follow-up

Participants continue to be monitored for progression-free survival and overall survival.

2 years
Follow-up visits every 6 months

Treatment Details

Interventions

  • Pembrolizumab
  • Young TIL
Trial Overview The trial is testing if adding pembrolizumab (an immunotherapy drug) to adoptive cell therapy using tumor infiltrating lymphocytes (TIL) plus IL-2 is safe and effective for shrinking melanoma tumors. Participants will receive chemotherapy followed by TIL infusion and possibly pembrolizumab.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: 3/ACT TIL (Pembro contraindicated)Experimental Treatment4 Interventions
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young TIL + highdose aldesleukin (IL-2)
Group II: 2/ACT TIL + PembroExperimental Treatment5 Interventions
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2) + pembrolizumab
Group III: 1/ACT TILExperimental Treatment4 Interventions
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2)

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a study of 107 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, a high number of stromal CD4 tumor-infiltrating lymphocytes (TILs) was linked to better progression-free survival (PFS) and overall survival (OS), indicating their potential as a prognostic marker.
Intratumoral CD8 TILs were also found to be significant predictors of overall survival, suggesting that both types of TILs could help identify which patients might benefit most from PD-1 blockade therapy.
Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer.Kaira, K., Yamaguchi, O., Kawasaki, T., et al.[2023]
In a study of 1017 melanoma patients, those with any type of tumor-infiltrating lymphocytes (TILs) showed higher rates of tumor regression and lower rates of sentinel lymph node positivity compared to those without TILs, suggesting that TILs may play a role in tumor response.
While brisk TILs (bTILs) were associated with better recurrence-free survival rates (84% at 5 years) compared to non-brisk (nbTILs) and absent TILs, there was no significant link between TIL status and disease-specific survival or response to immune checkpoint blockade therapy.
Prognostic Significance of Primary Tumor-Infiltrating Lymphocytes in a Contemporary Melanoma Cohort.Straker, RJ., Krupp, K., Sharon, CE., et al.[2023]
Prior treatments with anti-PD-1 and BRAF-targeted therapies showed limited effectiveness in activating tumor infiltrating lymphocytes (TIL) in patients with metastatic melanoma.
Understanding the mechanisms of action for TIL and anti-PD-1 therapies can help explain varying outcomes in clinical trials and guide the development of more effective cancer treatments.
TIL in Melanoma-Similar Approaches, Different Results, Unanswered Questions.Sznol, M.[2022]

References

Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer. [2023]
Prognostic Significance of Primary Tumor-Infiltrating Lymphocytes in a Contemporary Melanoma Cohort. [2023]
TIL in Melanoma-Similar Approaches, Different Results, Unanswered Questions. [2022]
Exposure to anti-PD-1 causes functional differences in tumor-infiltrating lymphocytes in rare solid tumors. [2020]
CD69 on Tumor-Infiltrating Cells Correlates With Neuroblastoma Suppression by Simultaneous PD-1 and PD-L1 Blockade. [2023]
Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial. [2020]
A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). [2020]
New developments in the management of advanced melanoma - role of pembrolizumab. [2020]
Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]
10.United Statespubmed.ncbi.nlm.nih.gov
Real-world experience with pembrolizumab in patients with advanced melanoma: A large retrospective observational study. [2022]
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