Immunotherapy + Adoptive Cell Therapy for Melanoma

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunosuppressive steroids

Disqualifiers: Active infections, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and benefits of a new cancer treatment that combines immune cells from the tumor, known as tumor infiltrating lymphocytes (TILs), with a drug called ipilimumab. Ipilimumab is a therapy that helps the immune system fight cancer. The trial targets individuals with advanced melanoma, a serious type of skin cancer, who have not previously received ipilimumab. Candidates should have melanoma that has spread and cannot be surgically removed, with some tumors remaining after previous treatments.

As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for advanced melanoma.

Do I need to stop my current medications to join 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 has shown that ipilimumab, the immunotherapy drug in this trial, has been widely studied for treating melanoma. In some studies, patients who took only ipilimumab had a 25% chance of surviving at both 2 and 3 years. However, ipilimumab can cause side effects like tiredness, diarrhea, and skin rash.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) is a newer treatment that uses certain immune cells to fight cancer. While specific safety details for TILs aren't provided, this pilot study is in the early testing stages, and researchers are closely monitoring for any side effects.

Overall, both treatments have shown promise in fighting melanoma, but like any medical treatment, they can have side effects. Participants should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Adoptive Cell Therapy with TIL (Tumor Infiltrating Lymphocytes) and Ipilimumab for melanoma because it offers a unique approach compared to existing treatments. While traditional therapies like chemotherapy and targeted drugs aim to kill cancer cells directly, this combination leverages the body's own immune system to fight the cancer. Adoptive Cell Therapy extracts and amplifies the patient's own TILs, which are then reinfused to attack the tumor, while Ipilimumab, an immune checkpoint inhibitor, enhances the immune response by blocking CTLA-4, a protein that downregulates the immune system. This dual approach not only targets the cancer more precisely but also has the potential to provide a more durable response.

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

Studies have shown that ipilimumab, a treatment that helps the immune system fight cancer, can benefit people with melanoma. It can delay cancer recurrence by about 9 months and reduce the risk of death by 28% compared to no treatment. Additionally, when combined with other treatments, 34% of patients experienced no cancer progression after 6 months. In this trial, participants will receive a combination therapy that includes ipilimumab, followed by lymphodepletion with chemotherapy, TIL infusion, and high-dose IL-2. Researchers are investigating tumor infiltrating lymphocytes (TILs), immune cells that can directly attack cancer cells. The combination of ipilimumab and TILs aims to strengthen the body's defense against melanoma, potentially offering a more effective fight against the cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

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 hasn't spread to more than three areas in the brain. They can't have had ipilimumab before but may have had other treatments. Participants need good organ function and performance status, not be pregnant, agree to use contraception, and cannot have certain medical conditions or a history of severe autoimmune disease.

Inclusion Criteria

I do not have serious heart rhythm problems.

All laboratory and imaging studies must be completed and satisfactory within 30 days of signing the consent document, with specific exceptions

My tumor may have a BRAF mutation, and I haven't been treated with ipilimumab.

Exclusion Criteria

My brain scans show no growth in my cancer 90 days after treatment for more than 3 or larger than 1 cm brain tumors.

I am taking immunosuppressive drugs for an autoimmune disease.

I am unable to understand and agree to the study's details.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Long-term Follow-up

Participants are monitored for progression-free survival

42 months

What Are the Treatments Tested in This Trial?

Interventions

• Administration of Lymphodepletion
• Adoptive Cell Therapy with TIL
• Cyclophosphamide as Part of Lymphodepletion
• Fludarabine as Part of Lymphodepletion
• High Dose IL-2
• Ipilimumab

Trial Overview The study tests combining TIL (a type of white blood cell) therapy with ipilimumab (an immunotherapy drug), along with lymphodepletion (lowering white blood cells), high dose IL-2 (a substance that activates immune cells), and adoptive cell transfer to see if this approach is safe and effective against melanoma.

How Is the Trial Designed?

Group I: Combination Therapy Experimental Treatment 7 Interventions

The combination of ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Iovance Biotherapeutics, Inc.

Industry Sponsor

Trials

26

Recruited

1,800+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a phase II clinical trial involving 31 patients with metastatic melanoma, adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) resulted in a 48.4% objective clinical response rate, with 6.5% of patients achieving complete remission.

The study found that a higher number of infused TIL, particularly those with a greater proportion of CD8(+) T cells and a more differentiated effector phenotype, were significantly associated with better tumor regression outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Radvanyi, LG., Bernatchez, C., Zhang, M., et al.[2022]

Ipilimumab, a monoclonal antibody targeting CTLA-4, has been shown to significantly improve overall survival in patients with metastatic melanoma, with a median survival of 10.1 months compared to 6.4 months for those receiving a vaccine alone in a phase III trial involving previously treated patients.

While ipilimumab offers a clear survival benefit, it is associated with serious immune-related adverse events in 10% to 15% of patients, necessitating careful monitoring and potential use of immune-suppressive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma. Lipson, EJ., Drake, CG.[2022]

Ipilimumab, an antibody that enhances T-cell activation, is effective for treating metastatic melanoma but can cause immune-mediated side effects, including rare cases of ileitis without colitis, as seen in a 54-year-old patient.

The study highlights the need for further research into genetic and epigenetic factors to personalize treatment and minimize adverse effects associated with ipilimumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab and immune-mediated adverse events: a case report of anti-CTLA4 induced ileitis. Venditti, O., De Lisi, D., Caricato, M., et al.[2018]

In a study of 56 patients with metastatic melanoma who had severe immune-related adverse events (AEs) from ipilimumab, 36% experienced at least one immune-related AE after receiving anti-PD-1 therapy, indicating a notable risk of recurrence but also a manageable safety profile.

Despite the risk of AEs, anti-PD-1 therapy showed a 43% overall response rate and a median overall survival of 21 months, suggesting it may offer improved outcomes for patients previously affected by severe toxic effects from ipilimumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Anti-Programmed Cell Death 1 Antibody Treatment With Risk of Recurrence of Toxic Effects After Immune-Related Adverse Events of Ipilimumab in Patients With Metastatic Melanoma. Brunot, A., Grob, JJ., Jeudy, G., et al.[2021]

Ipilimumab, an anti-CTLA-4 monoclonal antibody, significantly extends overall survival in patients with unresectable stage III or IV melanoma by enhancing T-cell activation and immune response against tumors.

While ipilimumab can lead to immune-related adverse events (irAEs), which are often manageable, proper management strategies are crucial to ensure patients can safely benefit from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-mediated adverse events associated with ipilimumab ctla-4 blockade therapy: the underlying mechanisms and clinical management. Tarhini, A.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12080919/

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in ... In patients who were progression-free at 3-years, 10-year melanoma-specific survival rates were 96% with nivolumab-plus-ipilimumab, 97% with ...

2. curemelanoma.org curemelanoma.org/patient-eng/melanoma-treatment/options/yervoy-ipilimumab

Ipilimumab, Yervoy - MRA The results showed that ipilimumab extended the amount of time before cancer returned by an average of 9 months.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2210233

Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in ... The estimates of 6-month progression-free survival were 34% (90% CI, 25 to 44) in the combination-treatment group and 13% (90% CI, 4 to 27) in ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)37101-7/fulltext

Efficacy and safety of ipilimumab in metastatic melanoma ... Survival rates at 2 and 3 years were 25% (24 of 95) and 25% (13 of 53) with ipilimumab alone and 19% (54 of 284) and 15% (24 of 156) with ipilimumab plus gp100.

5. news.bms.com news.bms.com/news/details/2016/Yervoy-ipilimumab-Improves-Overall-Survival-in-Fully-Resected-Stage-III-Melanoma-Patients-From-Phase-3-Study/default.aspx

Yervoy (ipilimumab) Improves Overall Survival in Fully ... Yervoy demonstrated a 28% reduction in the risk of death versus placebo in first disclosure of overall survival data from pivotal study ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa1611299

Prolonged Survival in Stage III Melanoma with Ipilimumab ... At a median follow-up of 2.7 years, adjuvant ipilimumab was associated with significantly prolonged recurrence-free survival, the primary end ...

7. news.bms.com news.bms.com/news/details/2024/Bristol-Myers-Squibb-Presents-Landmark-10-Year-Follow-Up-Data-from-CheckMate--067-Which-Showed-Continued-Durable-Long-Term-Survival-Benefit-with-Opdivo-plus-Yervoy-in-Advanced-Melanoma/default.aspx

067 Which Showed Continued Durable Long-Term ... With a minimum follow up of 10 years, median overall survival (OS) was 71.9 months with Opdivo plus Yervoy (95% CI: 38.2-114.4) - the longest ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02229

Long-Term Outcomes With Nivolumab Plus Ipilimumab or ... Durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab versus ipilimumab in patients with advanced melanoma.