BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study

Recruiting now · Phase 2

Conditions studied: Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Locally Recurrent Head and Neck Squamous Cell Carcinoma, Locally Recurrent Hypopharyngeal Squamous Cell Carcinoma, Locally Recurrent Laryngeal Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oropharyngeal Squamous Cell Carcinoma, Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma, Metastatic Laryngeal Squamous Cell Carcinoma, Metastatic Melanoma, Metastatic Oral Cavity Squamous Cell Carcinoma, Metastatic Oropharyngeal Squamous Cell Carcinoma, Recurrent Melanoma, Stage III Hypopharyngeal Carcinoma AJCC v8, Stage III Laryngeal Cancer AJCC v8, Stage III Lip and Oral Cavity Cancer AJCC v8, Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IV Hypopharyngeal Carcinoma AJCC v8, Stage IV Laryngeal Cancer AJCC v8, Stage IV Lip and Oral Cavity Cancer AJCC v8, Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Unresectable Melanoma

In brief

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.

Key facts

Study ID

NCT05136196

Run by

National Cancer Institute (NCI)

People needed

150

Starts

2022-12-06

Expected to finish

2027-01-01

Last updated by the study team

2026-08-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• STEP 1 - SPECIMEN SUBMISSION
• Participants must 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
• Note: For participants with primary oropharyngeal cancer, human papillomavirus (HPV) or p16 status must be known prior to step 1 registration
• Participants must have disease presentation consistent with measurable disease. Note: Current disease measurements will not be required until step 2 registration
• Participants must have had documented progression during or 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. 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 are considered unresectable
• Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test within 6 months prior to step 1 registration
• Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load within 28 days prior to step 1 registration
• Participants with a history of hepatitis C virus (HCV) infection must have no detectable viral load within 28 days prior to step 1 registration
• Participants must not have an active infection requiring systemic therapy (except HBV, HCV or HIV as mentioned above)
• Participants must not have experienced myocardial infarction or thromboembolic event requiring anticoagulation within 90 days prior to step 1 registration, unless clinically stable with ongoing medical management
• Participants must have recovered to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 toxicities related to any prior treatments, unless adverse events are deemed clinically nonsignificant by the treating investigator or stable on supportive therapy
• Participants must not have received more than one prior primary radiotherapy regimen, curative or adjuvant, to the mucosal surfaces of the head and neck, with the additional following criteria:
• If the primary radiation is combined with chemotherapy, a minimum of 16 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration. If the radiation is given alone, a minimum of 8 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration
• Additional palliative radiotherapy regimens are permitted but cannot have been administered to previously treated tissue (i.e., overlapping fields are excluded) with the exception of central nervous system (CNS) radiation and must be completed at least 4 weeks prior to step 1 registration
• Treatment areas should be healed with no sequelae from radiation therapy (RT) that would predispose to fistula formation
• Participants must not have received prior treatment with anti-VEGF therapies for any reason
• Participants must be >= 18 years of age
• Participants must have a Zubrod Performance Status 0 or 1
• Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and must be class 2B or better to be eligible for this trial
• Participants must not have any known significant organ disfunction that, in the opinion of the treating investigator, may impact suitability for receiving combination nivolumab/cabozantinib treatment
• Participants must be able to take oral medication without breaking, opening, crushing, dissolving or chewing capsules
• Participants must not have malabsorption syndrome
• Participants must not have active autoimmune disease requiring systemic steroids (equivalent of > 10mg of prednisone) or other immune suppression. Exceptions:
• Type 1 diabetes mellitus
• Endocrinopathy only requiring hormone replacement

Where it is running

• Saint Luke's Cancer Institute - Nampa — Nampa, Idaho, United States (enrolling)
• Tower Cancer Research Foundation — Beverly Hills, California, United States (enrolling)
• Kootenai Health - Coeur d'Alene — Coeur d'Alene, Idaho, United States (enrolling)
• Saint Alphonsus Cancer Care Center-Nampa — Nampa, Idaho, United States (enrolling)
• Cedars-Sinai Medical Center — Los Angeles, California, United States (enrolling)
• UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States (enrolling)
• UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care — Irvine, California, United States (enrolling)
• Mayo Clinic Hospital in Arizona — Phoenix, Arizona, United States (enrolling)
• Saint Luke's Cancer Institute - Fruitland — Fruitland, Idaho, United States (enrolling)
• Saint Luke's Cancer Institute - Meridian — Meridian, Idaho, United States (enrolling)
• Cancer Care and Hematology-Fort Collins — Fort Collins, Colorado, United States (enrolling)
• UCHealth Greeley Hospital — Greeley, Colorado, United States (enrolling)
• Medical Center of the Rockies — Loveland, Colorado, United States (enrolling)
• Helen F Graham Cancer Center — Newark, Delaware, United States (enrolling)
• Medical Oncology Hematology Consultants PA — Newark, Delaware, United States (enrolling)
• Mayo Clinic in Florida — Jacksonville, Florida, United States (enrolling)
• UCHealth Memorial Hospital Central — Colorado Springs, Colorado, United States (enrolling)
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States (enrolling)
• Memorial Hospital North — Colorado Springs, Colorado, United States (enrolling)
• The Angeles Clinic and Research Institute - West Los Angeles Office — Los Angeles, California, United States (enrolling)
• Poudre Valley Hospital — Fort Collins, Colorado, United States (enrolling)
• Saint Alphonsus Cancer Care Center-Boise — Boise, Idaho, United States (enrolling)
• Saint Luke's Cancer Institute - Boise — Boise, Idaho, United States (enrolling)
• Saint Alphonsus Cancer Care Center-Caldwell — Caldwell, Idaho, United States (enrolling)
• Kootenai Clinic Cancer Services - Post Falls — Post Falls, Idaho, United States (enrolling)

Full record on ClinicalTrials.gov

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