Nivolumab + Axitinib for Advanced Melanoma

Overseen By Amy Rose, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yana Najjar

Must not be taking: CYP3A4/5 inhibitors, CYP3A4/5 inducers

Disqualifiers: Hypertension, Heart failure, 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: 5

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, nivolumab (an immunotherapy drug) and axitinib (a targeted therapy drug), to evaluate their effectiveness for individuals with advanced melanoma (a type of skin cancer) that cannot be surgically removed. The goal is to determine if these drugs can benefit patients who have not responded to previous treatments. Participants receive nivolumab through an IV every four weeks and take axitinib pills twice daily for up to two years. Suitable candidates for this trial have melanoma that has progressed after previous treatments, particularly those involving anti-PD1 therapy, and have measurable disease that can be tracked. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people, offering hope for those seeking new options.

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

The trial does not specify if you need to stop all current medications, but you cannot use certain drugs that strongly affect liver enzymes, like some antibiotics and antifungals, or grapefruit products. If you're on these, you might need to stop them before joining the trial.

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

Research shows that the combination of nivolumab and axitinib is generally well-tolerated by patients with advanced melanoma. Studies have found that patients taking this combination usually experience manageable side effects. Common side effects include fatigue, diarrhea, and high blood pressure.

Earlier research indicated that serious side effects were less common, though some patients experienced liver problems and low blood cell counts. Adjusting the dose or temporarily stopping treatment managed these issues. Overall, the safety information suggests that while side effects can occur, they are often manageable with medical care. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Nivolumab and Axitinib together for advanced melanoma because this combination targets cancer in a new way. Nivolumab is an immunotherapy that boosts the body's immune system to attack cancer cells, offering a different approach than standard treatments like chemotherapy or single-agent targeted therapies. Axitinib, on the other hand, is a targeted therapy that inhibits pathways that tumors use to grow blood vessels, essentially starving the cancer. This dual approach could potentially enhance effectiveness by attacking the melanoma on multiple fronts, which might lead to better outcomes compared to existing therapies.

What evidence suggests that nivolumab plus axitinib could be an effective treatment for advanced melanoma?

Research has shown that using nivolumab and axitinib together may help treat advanced melanoma. In this trial, participants will receive this combination. One study found that it worked well for patients with advanced stages of the disease, especially those unresponsive to other treatments. Earlier research indicated that patients receiving these drugs lived longer overall. Specifically, the combination therapy improved two-year survival rates by 20% for some patients. This suggests that nivolumab and axitinib together could be a helpful option for people with advanced melanoma. ^{1 2 3 6 7}

Who Is on the Research Team?

Yana Najjar, MD

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with stage III or IV melanoma that worsened after anti-PD1 therapy, possibly with anti-CTLA4. They must have measurable disease, be able to perform daily activities (ECOG 0 or 1), and use birth control. Excluded are those with active TB, recent major surgery or radiation, certain heart conditions, uncontrolled hypertension, known allergies to the drugs tested, some prior severe side effects from similar treatments, and pregnant or breastfeeding individuals.

Inclusion Criteria

I am not pregnant, using birth control, sterile, or abstaining from sex for the study duration and 5 months after.

My melanoma cannot be removed by surgery and is not uveal melanoma.

My cancer worsened after treatment with anti-PD1, possibly with anti-CTLA4, confirmed by scans.

Exclusion Criteria

You are allergic to nivolumab or axitinib, or any of the ingredients in these medications.

I have severe heart failure.

I have HIV with specific CD4 count and viral load levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab 480 mg intravenously every 4 weeks and axitinib 5 mg twice daily by mouth for up to two years

Up to 2 years

Every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Axitinib
• Nivolumab

Trial Overview The study tests a combination of nivolumab (an immunotherapy drug) given intravenously every four weeks and axitinib (a cancer growth blocker) taken orally twice daily. Participants can receive these medications for up to two years unless they experience significant disease progression or intolerable side effects.

How Is the Trial Designed?

Group I: Nivolumab plus Axitinib Experimental Treatment 2 Interventions

Nivolumab 480mg, IV, every 4 weeks, for up to two years. Axitinib 5mg, PO, BID, for up to two years.

Axitinib is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Inlyta for:

• Renal cell carcinoma

Approved in United States as Inlyta for:

• Advanced renal cell carcinoma

Approved in United Kingdom as Inlyta for:

• Advanced renal cell carcinoma

Who Is Running the Clinical Trial?

Yana Najjar

Lead Sponsor

Trials

7

Recruited

200+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

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

Ipilimumab showed a best overall response rate (BORR) of 5.8% and a disease control rate (DCR) of 27% in patients with advanced melanoma, indicating some level of efficacy in this challenging population.

The treatment resulted in promising long-term survival rates, with 1- and 2-year survival rates of 47.2% and 32.8%, respectively, and a median overall survival of 10.2 months, while adverse events were primarily immune-related but manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. O'Day, SJ., Maio, M., Chiarion-Sileni, V., et al.[2022]

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]

In a phase 2 trial involving 142 patients with untreated advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 2-year overall survival rate of 63.8%, compared to 53.6% for those receiving ipilimumab alone, suggesting improved survival outcomes with the combination therapy.

However, the combination treatment was associated with a higher incidence of severe side effects, with 54% of patients experiencing grade 3-4 adverse events compared to 20% in the ipilimumab-only group, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Hodi, FS., Chesney, J., Pavlick, AC., et al.[2022]

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]

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]

The combination of nivolumab and relatlimab shows a manageable safety profile for patients with advanced melanoma who have already undergone treatment.

This combination therapy may offer a new option for patients with pretreated melanoma, suggesting potential efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab Is Safe and Efficacious in Pretreated Melanoma. [2023]

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]

In a real-world study of 709 patients with advanced melanoma treated with ipilimumab plus nivolumab, 50.7% experienced severe treatment-related adverse events, highlighting the need for careful monitoring during therapy.

Despite the high rate of adverse events, the combination therapy showed promising long-term survival outcomes, with a median overall survival of 28.7 months and a 4-year overall survival rate of 50% for patients similar to those in the CheckMate-067 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world Outcomes of Ipilimumab Plus Nivolumab Combination Therapy in a Nation-wide Cohort of Advanced Melanoma Patients in the Netherlands. van Zeijl, MCT., van Breeschoten, J., de Wreede, LC., et al.[2023]

Combining nivolumab with ipilimumab results in higher response rates in cancer treatment compared to using nivolumab alone, indicating a potentially more effective therapeutic strategy.

This combination therapy may enhance the immune response against cancer, but specific details on the number of subjects or study duration are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]

In a study of 697 patients with advanced melanoma treated with ipilimumab and nivolumab, the combination therapy showed a median overall survival of 53.7 months for treatment-naïve patients without brain metastases, indicating strong efficacy in this group.

However, the treatment was associated with significant toxicity, with 44% of patients experiencing grade 3-4 treatment-related adverse events and 0.7% experiencing treatment-related deaths, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world outcomes with ipilimumab and nivolumab in advanced melanoma: a multicentre retrospective study. Serra-Bellver, P., Versluis, JM., Oberoi, HK., et al.[2022]

In a study of 142 patients with advanced melanoma, the combination of nivolumab and ipilimumab resulted in a significantly higher objective response rate of 61% compared to 11% for ipilimumab alone, indicating that the combination therapy is much more effective for treating this type of cancer.

While the combination therapy showed promising efficacy, it also had a higher incidence of severe adverse events (54% vs. 24% for monotherapy), but most of these side effects were manageable with immune-modulating medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. Postow, MA., Chesney, J., Pavlick, AC., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.9555

Phase 2 study of axitinib + nivolumab in mucosal ... The frontline combination of nivolumab and axitinib was effective in patients with unresectable or advanced outside of China.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05384496

Axitinib and Nivolumab for the Treatment of Mucosal ... The researchers are doing this study to find out whether the combination of axitinib and nivolumab is an effective and safe treatment for people with advanced ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS9600

A phase II trial of nivolumab plus axitinib in patients with ... Real-world efficacy and safety data of anti-PD-1 plus anti-CTLA-4 combination therapy in Chinese patients with advanced melanoma.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1040842824000192

The treatment of advanced melanoma: Current approaches ... The study established that the sequence beginning with combination ipilimumab/nivolumab resulted in a 20% absolute improvement in 2-year overall survival (72% ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11373357/

Advances in immunotherapy for mucosal melanoma The median progression-free survival (PFS) was 1.4 months, the median overall survival (OS) was 12.0 months, and the one-year OS rate was 50.0%.

6. sciencedirect.com sciencedirect.com/science/article/pii/S0959804921004743

Real-world efficacy and safety of axitinib in combination ... The aim of this retrospective study was to evaluate the efficacy and safety of the combination regimen for advanced mucosal melanoma in the real world.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6448290/

Real-world efficacy and safety of nivolumab in previously ... At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7–6.2) and the 12-month overall survival rate ...