Nivolumab for Skin Cancer

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Must not be taking: Immunosuppressants, Steroids, Live vaccines

Disqualifiers: Active autoimmune, Pneumonitis, Pregnancy, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well nivolumab treats stage IIB-IIC melanoma, a type of skin cancer that can be surgically removed. Nivolumab, a monoclonal antibody, is designed to interfere with the growth and spread of cancer cells. It suits individuals who have undergone surgery to remove stage IIB-IIC melanoma from the skin and show no signs of cancer spreading elsewhere. Participants should be able to follow study instructions and have a history of melanoma that hasn't metastasized or originated from mucosal or ocular regions. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important advancements in melanoma treatment.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot be on immunosuppressive therapy with more than 10 mg/day of prednisone within 14 days of enrollment, and you must not have received live vaccines within 42 days prior to registration.

Is there any evidence suggesting that nivolumab is likely to be safe for humans?

Research has shown that nivolumab is generally well-tolerated by people with skin cancer. In earlier studies, it demonstrated strong effects against cancer and was well-received by patients with certain types of skin cancer. However, some patients experienced serious side effects. About 42% of patients reported severe reactions, though no single type of reaction was common.

Nivolumab is already approved for other types of cancer, indicating that its safety is well-understood. While side effects can occur, they are usually manageable. Prospective trial participants should discuss any concerns with the research team, who can explain what to expect and how to manage any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for melanoma?

Nivolumab is unique because it belongs to a class of treatments called immune checkpoint inhibitors, which are different from traditional chemotherapy or targeted therapy. It works by blocking the PD-1 pathway, which cancer cells use to hide from the immune system. This mechanism helps the immune system recognize and attack cancer cells more effectively. Researchers are excited about nivolumab because it has the potential to offer a more targeted approach with fewer side effects compared to conventional treatments like chemotherapy. Additionally, its ability to modulate the immune response offers hope for longer-lasting cancer control.

What evidence suggests that nivolumab might be an effective treatment for melanoma?

Research has shown that nivolumab, the treatment under study in this trial, effectively treats melanoma, a type of skin cancer. Studies found that patients taking nivolumab had a 43% lower chance of their cancer spreading, growing, or worsening compared to those receiving another treatment called YERVOY. In another study, 41% of people taking nivolumab did not see their cancer worsen for at least 24 weeks. Additionally, long-term data shows that 43% of patients treated with nivolumab and another drug, ipilimumab, were still alive ten years later, with many not needing more treatment. These findings support nivolumab's ability to help control melanoma. ^{3 4 6 7 8}

Who Is on the Research Team?

Takami Sato, MD, PhD

Principal Investigator

Sidney Kimmel Cancer Center at Thomas Jefferson University

Are You a Good Fit for This Trial?

This trial is for patients with stage IIB-IIC melanoma that can be surgically removed. They must have no metastatic disease, acceptable blood counts and organ function, and a good performance status (able to carry out daily activities). HIV-positive individuals may join if they meet certain criteria. Women who can bear children need a negative pregnancy test and must use birth control. Participants cannot have had certain prior treatments or live vaccines recently, nor active hepatitis or autoimmune diseases.

Inclusion Criteria

You can participate if you have HIV, but you need to meet certain requirements.

My sentinel lymph node biopsy was negative or the attempt to perform one failed.

I do not have an active hepatitis B or C infection.

Exclusion Criteria

I have not taken certain specified drugs or antibodies.

Treatment with any investigational agent within 14 days of first administration of study treatment is not permitted

I have not had any other cancer types, with certain exceptions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab IV over at least 30 minutes on day 1, repeated every 4 weeks for up to 12 courses

48 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab

Trial Overview The study is testing Nivolumab's effectiveness on early-stage melanoma suitable for surgery. Nivolumab is an antibody that might stop cancer cells from growing by interfering with their signals. The trial will see if this treatment prevents the spread of cancer after the tumor has been surgically removed.

How Is the Trial Designed?

Group I: Treatment (nivolumab) Experimental Treatment 1 Intervention

Patients receive nivolumab IV over at least 30 minutes on day 1. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Sidney Kimmel Cancer Center at Thomas Jefferson University

Lead Sponsor

Trials

164

Recruited

10,900+

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

Combining nivolumab and ipilimumab shows improved effectiveness in treating metastatic melanoma compared to using either drug alone, based on a retrospective analysis of approximately 7700 patients.

The combination therapy presents a safety profile that includes immune-related adverse events from both drugs, indicating that while the combination is effective, it also carries a heightened risk of toxicity that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. Soldatos, TG., Dimitrakopoulou-Strauss, A., Larribere, L., et al.[2022]

Over 40% of melanoma patients treated with anti-PD-1 therapy experience dermatologic immune-related adverse events (irAEs), but these are typically self-limiting and manageable, with common issues including rashes and itching.

Both anti-PD-1 and anti-PD-L1 antibodies show a similar dermatologic safety profile, and while these skin reactions are frequent, they rarely lead to severe complications or the need to stop treatment, highlighting the importance of early recognition and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies. Sibaud, V., Meyer, N., Lamant, L., et al.[2022]

Nivolumab (Opdivo) monotherapy led to complete regression of local recurrence and multiple lung metastases in a patient with recurrent skin melanoma and a positive BRAF mutation, demonstrating its efficacy as a treatment option.

After 5 courses of nivolumab, the patient experienced significant improvement in her condition, achieving an ECOG performance status of 0, indicating a return to an active lifestyle without pain, and normal serum LDH levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EVALUATION OF THE EFFICASY OF THE DRUG OPDIVO (NIVOLUMAB) IN A PATIENT DIAGNOSED WITH UNRESECTABLE SKIN MELANOMA, POSITIVE BRAF MUTATION AND DISEASE DISSEMINATION (CASE REPORT)]. Samsonia, M., Kandelaki, M., Gibradze, O., et al.[2021]

Nivolumab, a monoclonal antibody targeting the programmed death receptor-1, has shown promising efficacy in treating advanced malignant melanoma, with nearly 25% of patients achieving a partial tumor response in a phase II trial involving previously treated stage III/IV patients.

The treatment demonstrated a durable clinical benefit, with a median progression-free survival of 172 days and an acceptable safety profile, as less than 18% of patients experienced severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review of its use in patients with malignant melanoma. Deeks, ED.[2021]

Nivolumab, a PD-1 inhibitor used for advanced lung adenocarcinoma, can cause significant skin toxicity, as observed in a 60-year-old male patient who developed worsening skin rashes after treatment.

Early detection and treatment of immune-related skin toxicity with steroids led to alleviation of symptoms, suggesting that prompt management can improve patient outcomes while maintaining stable lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment-related Skin Toxicity Caused by Programmed Death-1 Inhibitor Nivolumab: A Case Report]. Gao, L., Yu, Y., Lu, S.[2020]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

Nivolumab is shown to be the most cost-effective treatment option for advanced melanoma patients in England, with incremental cost-effectiveness ratios of £24,483 for BRAF mutation-negative and £17,362 for mutation-positive patients.

The analysis utilized a Markov state-transition model based on patient-level data from clinical trials, indicating that nivolumab provides long-term survival benefits while being economically favorable compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Meng, Y., Hertel, N., Ellis, J., et al.[2020]

In a study of 37 patients with stage IV metastatic melanoma, high levels of soluble CD73 (sCD73) enzyme activity in the serum were linked to significantly poorer overall survival and progression-free survival when treated with nivolumab.

Patients with high sCD73 activity had a median progression-free survival of only 2.6 months compared to 14.2 months for those with lower activity, suggesting that measuring sCD73 could help predict how well patients will respond to nivolumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab. Morello, S., Capone, M., Sorrentino, C., et al.[2018]

Nivolumab significantly improved overall survival and progression-free survival in patients with unresectable or metastatic melanoma compared to dacarbazine, with hazard ratios of 0.42 and 0.43 respectively, based on a trial involving 418 patients.

The most common side effects of nivolumab included fatigue, diarrhea, and rash, but it was still considered to have a favorable benefit-risk profile compared to dacarbazine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. Beaver, JA., Theoret, MR., Mushti, S., et al.[2018]

Nivolumab, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. Wong, AC., Ma, B.[2018]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Citations

1. opdivohcp.com opdivohcp.com/efficacy/melanoma

Efficacy Data for Melanoma | OPDIVO® (nivolumab) In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In HCC ...

2. opdivo.com opdivo.com/melanoma/clinical-trial-results/advanced-immunotherapy

Advanced Melanoma Skin Cancer | Clinical Trial Results In the clinical trial, people given OPDIVO had a 43% lower risk of their cancer spreading, growing, or getting worse than those given YERVOY alone. More people ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.9528

Efficacy and safety of nivolumab for locally advanced or ... Conclusions: Nivolumab showed a robust antitumor-activity similar to other anti-PD-1 agents in advanced cSCC. Although ORR and OS were slightly ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4346215/

Nivolumab in melanoma: latest evidence and clinical potential Of note, 8 responding patients experienced transient tumor regression ranging from 1.9 to 5.6 months. Progression-free survival (PFS) at 24 weeks was 41%.

5. 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 ... “Remarkably, 43% of patients treated with nivolumab and ipilimumab are alive ten years later and many did not need subsequent therapy.” In ...

6. opdivohcp.com opdivohcp.com/safety/melanoma

Safety Profile for Melanoma | OPDIVO® (nivolumab) Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36274573/

A phase 2 study of first-line nivolumab in patients with ... Nivolumab resulted in robust antitumor activity, sustained responses, and good tolerability in systemic treatment-naive patients with aCSCC.

8. news.bms.com news.bms.com/news/details/2019/Five-Year-Outcomes-for-Opdivo-nivolumab-in-Combination-with-Yervoy-ipilimumab-Demonstrate-Durable-Long-Term-Survival-Benefits-in-Patients-with-Advanced-Melanoma/default.aspx

Five-Year Outcomes for Opdivo (nivolumab) in ... Five-year overall survival rates were 52% for the Opdivo plus Yervoy combination, 44% for Opdivo alone, and 26% for Yervoy alone.