This phase II trial studies the good and bad effects of the combination of drugs called cabozantinib and nivolumab in treating patients with melanoma or squamous cell head and neck cancer that has spread to other places in the body (advanced). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine how quickly patients can be divided into groups based on biomarkers in their tumors. A biomarker is a biological molecule found in the blood, other body fluids, or in tissues that is a sign of a normal or abnormal process or a sign of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. The two biomarkers that this trial is studying are "tumor mutational burden" and "tumor inflammation signature." Another purpose of this trial is to help doctors learn if cabozantinib and nivolumab shrink or stabilize the cancer, and whether patients respond differently to the combination depending on the status of the biomarkers.
1. Participants mustt have histologically confirmed melanoma that is stage III or IV, unresectable, recurrent, or metastatic non-uveal melanoma OR Participants must have histologically confirmed squamous cell carcinoma of the head and neck (HNSCC) that is either locally recurrent and non-amendable to curative therapy (e.g., radiation, surgery) or metastatic. The primary tumor location must be the oropharynx, oral cavity, hypopharynx, or larynx. Primary tumor site of nasopharynx (any histology) or unknown primary tumor are not eligible.
2. Participants must have disease presentation consistent with measurable disease.
3. Participants must have had documented progression within 12 weeks after the last dose of PD-1 checkpoint inhibition-based therapy. Participants must have been receiving checkpoint inhibition for a minimum of 6 weeks prior to progression. Participants who recur during adjuvant anti-PD1 treatment or within 12 weeks of completion of adjuvant anti-PD1 treatment are eligible if they have measurable disease and considered unresectable
1. Participants must not have an active infection requiring systemic therapy (except HBV, HCV or HIV).
2. Participants must not have received surgery, chemotherapy, radiation therapy, biologic agents, or steroids within 14 days prior to registration.
3. Participants must not have any known significant organ dysfunction that, in the opinion of the treating investigator, may impact suitability for receiving combination nivolumab/cabozantinib treatment
This study has a screening step to test your tumor to find out if it has high or low levels of “tumor mutational burden” and “tumor inflammation signature.” You will get treatment prior to receiving the biomarker results. You will get nivolumab through a vein in your arm on the first day of each cycle. Each cycle lasts 28 days. You will also take cabozantinib (a pill) by mouth every day. You will get treatment for up to 2 years or until the cancer begins to grow. CT or MRI must be repeated every 8 weeks for the first year, then every 12 weeks until the cancer grows and discontinuation of study treatment. After off treatment, follow-up will occur (with lab tests and scans performed as clinically indicated) every 12 weeks for up to a year and then every 6 months until 3 years have passes from the time you start the study. We expect to require 10-12 teaspoons of blood at each time point.