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

Trial Summary

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.

What data supports the effectiveness of the drug combination Axitinib and Nivolumab for treating melanoma?

Research shows that Nivolumab, a part of the combination, has demonstrated long-term survival benefits for advanced melanoma patients. Additionally, combining Nivolumab with another drug, Ipilimumab, has shown significant improvements in patient response and survival compared to using Ipilimumab alone. ^{1 2 3 4 5}

What safety information is available for the combination of Axitinib and Nivolumab in treating melanoma?

Nivolumab, used alone or in combination with other drugs, has been associated with side effects like fatigue, diarrhea, and skin reactions such as psoriasis. When combined with other treatments, it may increase the risk of immune-related side effects, but more studies are needed to fully understand its safety profile. ^{6 7 8 9 10}

How is the drug combination of Axitinib and Nivolumab unique for treating melanoma?

The combination of Axitinib and Nivolumab for melanoma is unique because it pairs a targeted therapy (Axitinib, which inhibits blood vessel growth in tumors) with an immune checkpoint inhibitor (Nivolumab, which helps the immune system attack cancer cells), potentially offering a novel approach compared to existing treatments that often use either type of drug alone. ^{1 2 3 5 11}

What is the purpose of this trial?

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 or metastatic mucosal melanoma that has not been treated before. The researchers think that a combination of axitinib and nivolumab may help people with this disease because both drugs target and block proteins that play a role in cancer cell survival and growth. The researchers think the drugs may be more effective if given in combination rather than on their own.

Research Team

Alexander Shoushtari

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Real-world outcomes with ipilimumab and nivolumab in advanced melanoma: a multicentre retrospective study. [2022]

4. England 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Psoriasis and psoriasiform reactions secondary to immune checkpoint inhibitors. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. [2022]

10. England 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. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Immunotherapy First for BRAF-Mutant Melanoma. [2022]