S2101, Biomarker Stratified CaboZantinib and NivOlumab- A Phase II Study of Combining Cabozantinib and Nivolumab in Participants with Advanced Solid Tumors (IO Refractory Melanoma or HNSCC) Stratified by Tumor Biomarkers - An ImmunoMATCH Pilot Study
Study Description
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 may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of 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.
Eligibility
KEY INCLUSION CRITERIA:
- Histologically confirmed melanoma that is Stage III or IV, unresectable, recurrent, or metastatic non-uveal melanoma OR histologically confirmed head & neck squamous cell carcinoma (HNSCC) either locally recurrent and non-amendable to curative therapy (e.g., radiation, surgery) or metastatic. Primary tumor location must be oropharynx, oral cavity, hypopharynx, or larynx
- Subjects with known human immunodeficiency virus (HIV) infection are eligible if they are on anti-retroviral therapy with an undetectable viral load within 6 months prior to Step 1 registration
- Subjects receiving any prior treatment must have recovered to baseline OR <= Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version 5 toxicities, unless determined clinically nonsignificant by Investigator OR stable on supportive therapy
- Zubrod Performance Status of 0 or 1
- Adequate cardiac and organ function as defined by protocol
- Subjects must be able to take oral medication WITHOUT breaking, opening, crushing, dissolving, or chewing capsules
- Subjects must have a history and physical examination performed within 28 days prior to Step 2 registration
- Subjects must continue to meet ALL protocol-defined eligibility for Step 1 registration prior to Step 2 registration
KEY EXCLUSION CRITERIA:
- Subjects with primary tumor site of nasopharynx or undetermined/unknown primary tumor site
- Any active infection that requires systemic therapy (with protocol-defined exceptions for Hepatitis B/C, or HIV)
- Myocardial Infarction or thromboembolic event requiring anticoagulation therapy within 90 days prior to Step 1 registration, unless determined to be clinically stable with ongoing management
- Receipt of more than 1 prior primary radiotherapy regimen, curative, or adjuvant, to the mucosal surfaces of the head & neck. If primary radiotherapy is combined with chemotherapy, a minimum of 16 weeks is required to have elapsed between end of radiotherapy and Step 1 registration. Additional palliative radiotherapy regimens are permitted but cannot have been administered to previously treated tissue, with the exception of central nervous system radiation, which must be completed at least 4 weeks prior to Step 1 registration.
- Subjects with known malabsorption syndrome
- Subjects with any active autoimmune disease requiring systemic steroids or other immunosuppression, with the exception of Type 1 Diabetes mellitus, endocrinopathy only requiring hormone replacement, skin disorders (e.g., psoriasis, alopecia, or vitiligo) not requiring systemic therapy, and conditions not expected to recur in the absence of an external trigger
- Subjects with any of the following criteria: prior carotid bleeding, tumors invading major vessels (e.g., carotid), central lung metastases that are cavitary, prior history of bleeding related to current head & neck cancer, history of hemoptysis, or tumor bleeding within 3 months prior to Step 1 registration
