TIL Therapy + Pembrolizumab for Skin Cancer

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Richard Wu

Must not be taking: Antibiotics, Corticosteroids, Immunosuppressants, others

Disqualifiers: Ocular melanoma, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, LN-144 (Lifileucel) and pembrolizumab, to determine their safety and effectiveness in shrinking tumors in people with advanced melanoma, a type of skin cancer that has spread. LN-144 is a biological therapy that uses living cells to target and destroy cancer cells, while pembrolizumab is an immunotherapy that helps the immune system attack cancer. This trial may suit individuals with stage IIIB-D or stage IV melanoma who haven't received prior therapy and have tumors measurable by scans or physical exams.

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 innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy or radiotherapy within 4 weeks before starting the trial, and you should not be on systemic corticosteroids or other immunosuppressive medications within 14 days before the study drug administration.

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

Research has shown that using lifileucel and pembrolizumab together for skin cancer may present some safety concerns. In studies, serious side effects included low blood platelet count in about 77% of patients, low red blood cell count in 50%, and fever with low white blood cell count in about 42%. These side effects are significant but common with many cancer treatments.

While these findings suggest some risks, they also indicate that the treatment is under active study for its potential to combat advanced melanoma. Ongoing research aims to balance these risks with possible benefits for patients. Consulting a healthcare professional is important to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Lifileucel and Pembrolizumab for treating skin cancer because it represents a novel approach compared to existing treatments like surgery, radiation, and chemotherapy. Lifileucel is a type of TIL (tumor-infiltrating lymphocyte) therapy, which uses the patient’s own immune cells to target and attack cancer cells more effectively. This personalized immunotherapy is paired with Pembrolizumab, an immune checkpoint inhibitor that enhances the body’s immune response against cancer. Together, they offer a promising strategy that may improve outcomes by directly harnessing and boosting the body’s natural defenses.

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

Research has shown that combining lifileucel and pembrolizumab, the treatment under study in this trial, may effectively treat advanced melanoma. Lifileucel uses a patient's own immune cells to help shrink tumors. When combined with pembrolizumab, a drug that boosts the immune system to fight cancer, studies found that about 67% of patients who had not previously received immune checkpoint inhibitors experienced tumor shrinkage. This suggests that the combination could be a strong option for managing melanoma. ^{1 3 5 6 7}

Who Is on the Research Team?

Richard C Wu, M.D. Ph.D.

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults aged 18-75 with Stage IIIB-D or IV melanoma, accessible for tumor removal and no prior treatments. Must have good performance status, life expectancy over 3 months, and adequate organ function. Women must not be pregnant/breastfeeding; participants need to use contraception.

Inclusion Criteria

I can care for myself and doctors expect me to live 3 months or more.

I have a tumor in my lymph node that can be measured and accessed for treatment.

I have another cancer type, but it won't affect this trial's treatment.

Exclusion Criteria

My lung function test shows less than 60% of the normal breathing capacity.

I am an adult under legal guardianship or trusteeship.

You have tested positive for HTLV1/HTLV2 or syphilis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive pembrolizumab, cyclophosphamide, fludarabine, and lifileucel, followed by surgery

12 weeks

Multiple visits for drug administration and surgery

Maintenance

Participants receive pembrolizumab every 6 weeks for up to 1 year

1 year

Visits every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Lifileucel
• Pembrolizumab

Trial Overview The trial is testing LN-144 (Lifileucel) combined with pembrolizumab against advanced melanoma. Lifileucel uses living organism substances to target cancer cells while pembrolizumab boosts the immune system's response to cancer.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab, lifileucel) Experimental Treatment 5 Interventions

Patients receive pembrolizumab IV on day -14, cyclophosphamide IV QD on days -7 to -6, fludarabine IV over 30 minutes QD on days -5 to -1, and lifileucel IV infusion on day 0. Patients also receive pembrolizumab IV on day 28 and 70, and undergo surgery on day 80. MAINTENANCE: Patients receive pembrolizumab IV every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

Lifileucel is already approved in United States for the following indications:

Approved in United States as Lifileucel for:

• Unresectable or metastatic melanoma in adults who have previously been treated with a PD-1 inhibitor and, if BRAF-positive, a BRAF inhibitor with or without a MEK inhibitor

Who Is Running the Clinical Trial?

Richard Wu

Lead Sponsor

Trials

1

Recruited

2+

Iovance Biotherapeutics, Inc.

Industry Sponsor

Trials

26

Recruited

1,800+

Published Research Related to This Trial

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

In a study with 882 patients over a median follow-up of 45 months, pembrolizumab and pembrolizumab-chemotherapy showed significant improvements in overall survival compared to cetuximab-chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma, particularly in patients with high PD-L1 expression (CPS ≥ 20).

The analysis also indicated that patients who received pembrolizumab-based therapies had favorable outcomes in subsequent treatments, with improved progression-free survival on next-line therapies, highlighting the long-term efficacy of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington, KJ., Burtness, B., Greil, R., et al.[2023]

In a phase 1a/b trial involving 26 patients with PD-L1-positive non-small cell lung cancer (NSCLC), the combination of ramucirumab and pembrolizumab showed a manageable safety profile, with 84.6% experiencing treatment-related adverse events, primarily hypertension.

The treatment demonstrated promising efficacy, with an objective response rate of 42.3%, and particularly strong results in patients with high PD-L1 expression (TPS ≥ 50%), who had a median progression-free survival that was not reached.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. Herbst, RS., Arkenau, HT., Bendell, J., et al.[2023]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

A review of 29 articles identified specific dermatological adverse events (AEs) associated with various immunotherapy combinations, highlighting that combinations like nivolumab/ipilimumab and lenvatinib/pembrolizumab had the highest incidence of rash.

Understanding these dermatological AEs, such as pruritus and alopecia, is crucial for optimizing treatment plans and improving patient monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. Salloum, A., Habre, M., Chebl, JA., et al.[2022]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

In a study of 355 patients with metastatic melanoma resistant to anti-PD-(L)1 therapy, combining ipilimumab with anti-PD-1 (either pembrolizumab or nivolumab) resulted in a significantly higher objective response rate (31%) compared to ipilimumab alone (13%).

Patients receiving the combination therapy also experienced longer overall survival (20.4 months vs. 8.8 months) and longer progression-free survival (3.0 months vs. 2.6 months), while the rates of severe adverse events were similar between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab alone or ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study. Pires da Silva, I., Ahmed, T., Reijers, ILM., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a Phase 2 trial involving 153 patients with advanced melanoma who had previously progressed on immune checkpoint inhibitors, lifileucel showed an objective response rate (ORR) of 31.4%, indicating its potential effectiveness in this challenging patient population.

The treatment demonstrated durable responses, with 41.7% of patients maintaining their response for at least 18 months, and a favorable safety profile, although common severe side effects included thrombocytopenia and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study. Chesney, J., Lewis, KD., Kluger, H., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9505

Efficacy and safety of lifileucel, an autologous tumor- ... These results demonstrate encouraging efficacy and durability for the combination of lifileucel and pembro and support its further evaluation in pts with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36600653/

Efficacy and safety of lifileucel, a one-time autologous tumor ... Investigational lifileucel demonstrated clinically meaningful activity in heavily pretreated patients with advanced melanoma and high tumor burden.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS9607

A phase 3 study (TILVANCE-301) to assess the efficacy ... Earlier-line treatment with lifileucel plus pembrolizumab (pembro) in pts with ICI-naïve advanced melanoma demonstrated an ORR of 67%, including ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06538012

Study Details | NCT06538012 | TIL Therapy Combined ... Lifileucel (Amtagvi), the first FDA-approved TIL therapy, has demonstrated significant success in treating unresectable or metastatic melanoma by utilizing the ...

5. curemelanoma.org curemelanoma.org/blog/the-tilvance-301-trial-expanding-a-patients-own-tumor-fighting-cells-to-generate-a-long-term-response-in-advanced-melanoma

The TILVANCE-301 Trial: Expanding a Patient's Own ... The goal of TILVANCE-301 is to understand more about the safety of lifileucel in combination with pembrolizumab compared to pembrolizumab alone ...

6. ejcskn.com ejcskn.com/article/S2772-6118(25)00345-3/fulltext

Efficacy and safety of lifileucel, an autologous tumor- ... Conclusions: These results support further evaluation of lifileucel and pembrolizumab as frontline treatment for advanced melanoma in the phase 3 TILVANCE-301 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05727904

NCT05727904 | Study to Investigate Lifileucel Regimen ... This is a Phase 3, multicenter, open-label, randomized, parallel group, treatment study to assess the efficacy and safety of lifileucel in combination with ...