Axitinib + Nivolumab for Melanoma

Recruiting at 1 trial location

Overseen By Christopher Barker, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, Cardiovascular disease, 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: Unknown

Duration: 104 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial assesses whether a combination of two drugs, axitinib (Inlyta) and nivolumab (Opdivo), can effectively and safely treat mucosal melanoma, a specific type of skin cancer that has spread or cannot be surgically removed. These drugs block proteins that help cancer cells survive and grow. The trial seeks participants with this melanoma in areas such as the head, neck, digestive, or urinary tracts who have not received prior treatment for it. Participants must have measurable disease that can be monitored and should not have received previous systemic treatment for their cancer. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic treatments like corticosteroids or immunosuppressive medications, you may need to stop them 14 days before starting the trial drugs.

Is there any evidence suggesting that the combination of axitinib and nivolumab is likely to be safe for humans?

Studies have shown that using axitinib and nivolumab together can help treat mucosal melanoma, a type of skin cancer. This combination has been tested in real-world settings, and many patients have tolerated the treatment well. Common side effects include fatigue, diarrhea, and high blood pressure. While these side effects can usually be managed, some people might experience more serious reactions, so doctors will monitor participants closely.

Axitinib is already approved for treating kidney cancer, suggesting it is relatively safe. Nivolumab, an immunotherapy used for several cancers, indicates it is generally well-tolerated. These drugs together seem promising, but like all treatments, they may have risks. Researchers will closely monitor participants to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Axitinib and Nivolumab for mucosal melanoma because it offers a novel approach by combining a VEGF receptor inhibitor (Axitinib) with an immune checkpoint inhibitor (Nivolumab). Unlike traditional treatments, which often involve surgery or chemotherapy, this combination targets both the tumor's blood supply and its ability to evade the immune system. This dual action could potentially enhance the body's capacity to fight the cancer more effectively and is especially promising for patients with advanced or inoperable forms of the disease.

What evidence suggests that the combination of axitinib and nivolumab might be an effective treatment for mucosal melanoma?

Research has shown that combining axitinib and nivolumab may help treat advanced mucosal melanoma. In this trial, participants will receive this combination as frontline therapy. These drugs block proteins that aid cancer cell growth, and they might work better together than individually. In previous studies, some patients experienced tumor shrinkage or disappearance, while others saw their disease stop progressing, indicating various positive responses. This combination could offer hope for improved outcomes in patients with this challenging type of melanoma. ^{1 2 3 5 6}

Who Is on the Research Team?

Alexander Shoushtari

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced mucosal melanoma that hasn't been treated before can join this trial. They should have a certain type of tumor, be in good enough health to perform daily activities (ECOG 0-2), and not be pregnant or breastfeeding. Participants must agree to use two contraception methods if applicable. People with severe allergies to the drugs, autoimmune diseases needing steroids, recent heart issues, or specific blood disorders cannot join.

Inclusion Criteria

My melanoma cannot be removed by surgery and started in specific areas like the mouth, nose, or genitals.

I have not had any systemic therapy for my condition before joining this study.

I am using two effective birth control methods and will continue for 23 weeks after my last treatment dose.

Exclusion Criteria

I have had heart issues within a specific timeframe.

I don't have current bleeding issues or recent serious blood clots.

I am currently receiving treatment for another cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab IV 480mg every 4 weeks plus axitinib 5mg twice daily. Upon progression, SBRT or ipilimumab may be added.

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue treatment with nivolumab and axitinib if they show good tolerance and progression

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Axitinib
• Nivolumab

Trial Overview The study is testing whether axitinib combined with nivolumab is effective for treating advanced mucosal melanoma. Axitinib blocks cancer cell growth signals while nivolumab boosts the immune system's response against cancer cells. The hope is that together they work better than alone.

How Is the Trial Designed?

Group I: Axitinib and Nivolumab for the Treatment of Mucosal Melanoma Experimental Treatment 3 Interventions

This is a single center trial enrolling up to 20 total evaluable patients with unresectable primary or advanced mucosal melanomas arising from the head and neck, gastrointestinal, or genitourinary tract to receive frontline therapy with nivolumab IV 480mg q4 weeks plus axitinib 5mg PO twice daily. A Simon 2-stage design will be utilized. Upon progression with good tolerance, addition of stereotactive body radiation therapy (SBRT) or CTLA-4 blockade to continued nivolumab plus axitinib will be offered to patients depending on the type of progression. For patients with local or oligometastatic progression, stereotactic body radiotherapy (SBRT) will be added; for patients with progression in a site of prior radiotherapy or with multifocal or distant progression not amenable to SBRT, ipilimumab 1mg/kg IV q3 weeks for up to 4 doses will be added.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

Published Research Related to This Trial

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 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]

Patients with newly diagnosed BRAFV600-mutant metastatic melanoma have better survival rates at 2 years when treated with the combination of immunotherapies nivolumab and ipilimumab compared to targeted therapies dabrafenib and trametinib.

These findings suggest that the combination of nivolumab and ipilimumab may establish a new standard for first-line treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy First for BRAF-Mutant Melanoma. [2022]

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 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]

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]

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]

A study analyzing 8213 reports of skin-related adverse drug reactions linked to immune checkpoint inhibitors found that 3.8% of these reports involved psoriasis or psoriasiform reactions, highlighting a significant safety concern.

Most patients (70.8%) who developed psoriasis had a pre-existing condition, indicating that those with a history of psoriasis may be at higher risk when treated with immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psoriasis and psoriasiform reactions secondary to immune checkpoint inhibitors. Cutroneo, P., Ingrasciotta, Y., Isgrò, V., et al.[2021]

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]

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

Real-world efficacy and safety of axitinib in combination ... Pembrolizumab plus lenvatinib have shown clinical benefit for advanced melanoma in phase I and II trials with ORRs of 21.4–48%, which has led to a phase III ...

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

Advances in immunotherapy for mucosal melanoma One patient achieved complete remission, three attained partial remission, and five experienced stable disease.

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

A phase II trial of nivolumab plus axitinib in patients with ... We previously showed that low dose axitinib reduces ITH in B16 murine mel, and our pre-clinical data show that axitinib synergizes with ICI to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9066368/

Toripalimab plus axitinib in patients with metastatic mucosal ... Axitinib in combination with toripalimab, a humanized IgG4 mAb against PD-1, showed a promising response rate in patients with metastatic mucosal melanoma (MM) ...