This phase Ib trial studies the side effects of nivolumab and to see how well it works alone and in combination with other treatments, such as ipilimumab, cabozantinib, platinum containing therapy, and fluoropyrimidine, in treating patients with autoimmune disorders and cancer that has spread from where it first started (primary site) to nearby tissue, lymph nodes, or distant parts of the body (advanced), to other places in the body (metastatic) or cannot removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib blocks certain proteins, which may help keep tumor cells from growing. It may also prevent the growth of new blood vessels that tumors need to grow. Cabozantinib is a type of tyrosine kinase inhibitor and a type of angiogenesis inhibitor. Chemotherapy drugs, such as platinum containing therapies and fluoropyrimidine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab alone and in combination with other treatments, including ipilimumab, cabozantinib, platinum containing therapy, or fluoropyrimidine, may be safe, tolerable, and/or effective in treating patients with autoimmune disorders and advanced, metastatic, or unresectable cancer.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
Patients can have either histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable, or have a malignancy for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting, as well as the neoadjuvant or perioperative setting in which such treatment is considered standard of care or has been approved. Eligible tumor types include solid tumors and malignancies in which there is known evidence of clinical activity for single agent PD-1 or PD-L1 antibodies. Nivolumab or other PD1/PD-L1 inhibitors are FDA-approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC), gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any solid tumor with microsatellite instability (MSI)-high status confirmed. Patients with HL are eligible but must follow standard response criteria. Additional tumor types may be eligible on a case by case basis upon discussion with principal investigator (PI)
Patients enrolling on the trial for adjuvant use will be restricted to those with histology for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC, cervical cancer, and bladder cancer
Patients enrolled on the study can receive Nivolumab with other FDA-approved combinations according to the FDA package insert, including, but not limited to ipilimumab, cabozantinib or chemotherapy
Patients who have previously received other forms of immunotherapy (high-dose [HD] IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine immunotherapy for at least 4 weeks before nivolumab administration. Patients who have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks
Disqualifiers
Repeat imaging demonstrates no new sites of bone metastases
The lesion being considered for palliative radiation is not a target lesion
Patients with prior therapy with an anti-PD-1 or anti-PD-L1
Patients with prior allogeneic hematologic transplant
Trial design
Design model
Parallel
Treatments tested in this trial
Biospecimen Collection
Procedure/Surgery
Undergo collection of blood, CSF, tissue, stool and urine samples
Cabozantinib
Drug
Given PO
Fluoropyrimidine
Drug
Given fluoropyrimidine
Ipilimumab
Biological/Vaccine
Given IV
Nivolumab
Biological/Vaccine
Given IV
Platinum Compound
Drug
Given platinum containing chemotherapy
Platinum Doublet
Drug
Given platinum doublet
Treatment groups
300 Participants
are divided into 11 treatment groups
11
Treatment groups
See each treatment group below.
Group A: Arm I (nivolumab)Experimental treatment 2 interventions
Group B: Arm II (nivolumab, ipilimumab)Experimental treatment 3 interventions
Group C: Arm III (nivolumab, platinum doublet)Experimental treatment 3 interventions
Group D: Arm IV (nivolumab, ipilimumab)Experimental treatment 3 interventions
Group E: Arm IX (nivolumab, ipilimumab)Experimental treatment 3 interventions
Group F: Arm V (nivolumab, ipilimumab, platinum doublet therapy)Experimental treatment 4 interventions
Group G: Arm VI (nivolumab, ipilimumab)Experimental treatment 3 interventions
Group H: Arm VII (nivolumab, ipilimumab, cabozantinib)Experimental treatment 4 interventions
Group I: Arm VIII (nivolumab, ipilimumab)Experimental treatment 3 interventions
Group J: Arm X (nivolumab, fluoropyrimidine, platinum, ipilimumab)Experimental treatment 5 interventions
Group K: Arm XI (nivolumab, fluoropyrimidine, platinum)Experimental treatment 4 interventions
Trial outcomes
Primary outcomes
1
Incidence of adverse events
Will be reported overall and by severity, and dose limiting toxicities will be summarized for all patients and by disease severity cohort.
Time frame
Up to 100 days after completion of study treatment
2
Change in disease assessments
Will be summarized at each time point for each disease severity cohort.
Time frame
Baseline up to 100 days after completion of study treatment
3
Overall response rate
Will be computed along with its associated exact 95% confidence interval for all patients and by disease severity cohort.
Time frame
Up to 5 years after completion of study treatment
4
Changes in serum chemokines and circulating immune cells over time
Will be summarized and assessed using generalized linear mixed modeling.
Time frame
Baseline up to 100 days after completion of study treatment
Secondary outcomes
Other outcomes
Sponsors and contacts
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