TIL + Pembrolizumab for Melanoma

Recruiting at 1 trial location

Overseen By NCI/Surgery Branch Recruitment Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Steroids, Investigational agents

Disqualifiers: Pregnancy, Immunodeficiency, Infections, Autoimmune, 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: 10

Duration: 4-6 weeks

170 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding the drug pembrolizumab to cell therapy can effectively shrink melanoma tumors. Researchers are testing this combination to assess its safety and efficacy compared to cell therapy alone. The trial involves individuals with metastatic melanoma of the skin who have undergone at least one previous treatment. Participants will undergo various screenings and treatments, including a hospital stay for chemotherapy and cell infusions. Those who have battled metastatic melanoma and received prior treatment might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

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.

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

Previous studies have shown that TIL therapy is safe for patients with advanced melanoma. A review of several studies examined the safety of TIL therapy combined with high-dose aldesleukin (a type of immune therapy) and confirmed its safety for patients.

Pembrolizumab, also tested in this trial, has a well-established safety record. The FDA has approved it for treating advanced melanoma, and it has been used successfully for many years. Some patients experience side effects, such as tiredness or skin problems, but serious side effects are less common.

When considering joining this trial, it is important to know that both treatments have shown promise in past research. They are generally well-tolerated, but like any treatment, they can have side effects. Always discuss potential risks and benefits with a healthcare provider before deciding to participate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for melanoma because they harness the power of tumor-infiltrating lymphocytes (TIL), which are immune cells extracted from the patient’s own tumor. Unlike standard melanoma treatments like targeted therapy and traditional immunotherapy, these experimental approaches involve expanding these TILs in the lab and reintroducing them to the patient, potentially enhancing the body’s ability to attack cancer cells. One arm of the trial combines these TILs with pembrolizumab, a well-known immunotherapy drug, to further boost the immune response. This innovative approach could lead to more personalized and effective treatment options for patients with melanoma.

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

Research shows that tumor-infiltrating lymphocyte (TIL) therapy, which participants in this trial may receive, can help treat advanced skin cancer, known as metastatic melanoma. Studies have found that TIL therapy can shrink tumors in 30% to 50% of patients who have tried other treatments. Another treatment tested in this trial is pembrolizumab. Research indicates that more than one-third of patients with advanced melanoma were still alive ten years after receiving pembrolizumab. Additionally, pembrolizumab helped stop the cancer from worsening in 43% of patients, outperforming treatments like ipilimumab. This trial will also explore the combination of TIL therapy and pembrolizumab, which may enhance their effectiveness, potentially shrinking tumors more effectively. ^{1 5 6 7 8}

Who Is on the Research Team?

Stephanie L Goff, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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

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)

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: 3/ACT TIL (Pembro contraindicated) Experimental Treatment 4 Interventions

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young TIL + highdose aldesleukin (IL-2)

Group II: 2/ACT TIL + Pembro Experimental Treatment 5 Interventions

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2) + pembrolizumab

Group III: 1/ACT TIL Experimental Treatment 4 Interventions

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a real-world study of 532 patients with advanced melanoma treated with pembrolizumab, the median overall survival was 21.8 months, indicating its effectiveness outside of clinical trials.

Patients with better performance status (ECOG 0-1), normal LDH levels, and no recent corticosteroid use had significantly improved overall survival, highlighting the importance of these factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab in patients with advanced melanoma: A large retrospective observational study. Liu, FX., Ou, W., Diede, SJ., et al.[2022]

In the GEM-Pembresid trial, pembrolizumab was tested as a consolidation treatment in multiple myeloma patients with persistent disease, but it only resulted in a decrease in M-protein in 1 out of 17 patients, indicating limited efficacy in this population.

While pembrolizumab had an acceptable safety profile, with some adverse events leading to treatment discontinuation, it did not enhance treatment responses, suggesting that it may not be beneficial as a consolidation therapy for patients with persistent measurable disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial. Puig, N., Corchete-Sánchez, LA., Pérez-Morán, JJ., et al.[2020]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Significance of Primary Tumor-Infiltrating Lymphocytes in a Contemporary Melanoma Cohort. Straker, RJ., Krupp, K., Sharon, CE., et al.[2023]

In a study using both immune-deficient nude mice and normal A/J mice, the use of anti-PD-1 and anti-PD-L1 antibodies effectively suppressed tumor growth in A/J mice, highlighting the critical role of T lymphocytes in the antitumor immune response.

The research found that increased infiltration of activated CD8+ tumor-infiltrating lymphocytes (TILs) was associated with smaller tumor sizes, suggesting that enhancing CD8+ TIL infiltration could be a promising strategy for treating neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD69 on Tumor-Infiltrating Cells Correlates With Neuroblastoma Suppression by Simultaneous PD-1 and PD-L1 Blockade. Inoue, S., Takeuchi, Y., Horiuchi, Y., et al.[2023]

In a Phase II clinical trial involving 22 patients with rare solid tumors, one dose of the anti-PD-1 antibody pembrolizumab led to increased CTLA-4 expression in CD4+ tumor-infiltrating lymphocytes (TIL), indicating a potential change in TIL phenotype after treatment.

However, the CD8+ TIL population showed a reduced ability to secrete cytokines post-treatment, suggesting that while PD-1 blockade may alter TIL characteristics, it could also impair their functional response in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure to anti-PD-1 causes functional differences in tumor-infiltrating lymphocytes in rare solid tumors. Creasy, CA., Forget, MA., Singh, G., et al.[2020]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TIL in Melanoma-Similar Approaches, Different Results, Unanswered Questions. Sznol, M.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Pembrolizumab is a monoclonal antibody that blocks the PD-1/PD-L1 interaction, which is crucial for preventing the immune system from attacking tumors, making it a key player in cancer immunotherapy.

It has been approved by the FDA for treating patients with advanced melanoma who have not responded to previous treatments, highlighting its efficacy in managing difficult cases of this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the management of advanced melanoma - role of pembrolizumab. Improta, G., Leone, I., Donia, M., et al.[2020]

In a study of 103 Chinese patients with advanced melanoma, pembrolizumab demonstrated a 16.7% objective response rate, indicating its effectiveness as a second-line treatment, particularly in aggressive melanoma subtypes.

The treatment was well tolerated, with 84.5% of patients experiencing treatment-related adverse events, but only a small percentage (8.7%) had severe side effects, and no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). Si, L., Zhang, X., Shu, Y., et al.[2020]

Citations

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Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ... At 10 years, more than one-third (34.0%) of patients with advanced melanoma were alive after treatment with KEYTRUDA, compared to 23.6% of patients treated ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10419154/

Efficacy of Pembrolizumab in Advanced Melanoma The results were comparable to those of nivolumab, showing a 5-year OS of 41% and 43%, respectively, in the two trials [34].

3. keytruda.com keytruda.com/melanoma/advanced/

is an fda-approved treatment for advanced melanoma The cancer did not progress in 43% of people who received KEYTRUDA compared to 32% of people who received ipilimumab. More people saw tumors shrink.

4. investors.iobiotech.com investors.iobiotech.com/news-events/news/news-details/2025/IO-Biotech-Presents-Phase-3-Results-for-Cylembio-plus-KEYTRUDA-pembrolizumab-in-First-line-Advanced-Melanoma-at-ESMO-2025/default.aspx

News Details Cylembio plus pembrolizumab achieved a clinically relevant 19.4 months median progression free survival (mPFS) compared to 11.0 months mPFS ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01704287

NCT01704287 | Study of Pembrolizumab (MK-3475) ... This study was conducted to compare survival using pembrolizumab (SCH 900475, MK-3475) or standard chemotherapy in participants with advanced melanoma (MEL)

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30715153/

Five-year survival outcomes for patients with ... - PubMed - NIH Background: Pembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03553836

NCT03553836 | Safety and Efficacy of Pembrolizumab ... This 2-part study will evaluate the safety and efficacy of pembrolizumab (MK-3475) compared to placebo in participants with surgically resected high-risk ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924000066

Safety profile of pembrolizumab monotherapy based on an ... Grade 3−5 AEs occurred in 50.6% of patients. AEs led to pembrolizumab discontinuation in 12.7% of patients and death in 5.9%. Immune-mediated AEs and infusion ...