UNISoN / ANZUP1602: This Phase II trial is evaluating two new immunotherapy treatments (Nivolumab and Ipilimumab) for patients with metastatic Non-Clear Cell Renal Cell CarcinomaA Phase II Sequential Treatment Trial of Single Agent Nivolumab, Then Combination Ipilimumab + Nivolumab in Metastatic or Unresectable Non-Clear Cell Renal Cell Carcinoma

Exclusion

1. Urothelial or transitional cell carcinoma of the renal pelvis or ureter
2. Predominant clear cell renal cell carcinoma. A minority of clear cell histology (<50%) is acceptable, but there must be >50% non-clear cell histology predominant.
3. Participation in a study of an investigational agent within 30 days of registration.
4. Prior treatment with nivolumab, ipilimumab, or with any other anti-PD-1, anti-PD-L1, Anti-PD-L2, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways (NB Participant is eligible for Part 2 of the study if they took nivolumab monotherapy in Part 1 of the study).
5. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
6. Any condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone or equivalent dose of alternative corticosteroid) or other immunosuppressive medications within 14 days of registration. Intranasal, inhaled or topical steroids are permitted in the absence of active autoimmune disease. Participants are permitted to enrol if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
7. Untreated brain or leptomeningeal metastases or current clinical or radiological progression of known brain metastases or requirement for steroid therapy for brain metastases. Participants with treated brain metastases are eligible if they have been stable and off steroids for ≥ 3 weeks.
8. Prior allogeneic organ transplant, inflammatory bowel disease, pneumonitis, tuberculosis, or primary immunodeficiency
9. Active infection requiring systemic therapy within 14 days before registration.
10. Receipt of live attenuated vaccination within 30 days of registration.
11. Life expectancy of less than 3 months.

12. Prior systemic therapy, surgery or radiation therapy within 4 weeks before registration.

    Note: If the participant has undergone major surgery, they must have recovered adequately before registration. Prior treatments with radiation therapy in the adjuvant and/or metastatic setting is permitted provided that therapy and is completed at least 14 days prior to the first dose of study drug and all treatment related adverse events are < Grade 1 at the time of registration.

13. History of another active malignancy within the previous 5 years, except for locally curable cancers that have been apparently cured, such as low-grade thyroid carcinoma, prostate cancer not requiring treatment (Gleason grade ≤ 6), basal or squamous cell skin cancer, superficial bladder cancer, melanoma in situ or carcinoma in situ of the prostate, cervix, or breast. Participants who have been free of other malignancies for ≥ 5 years prior to registration are eligible for this study.
14. Positive test for hepatitis B virus surface antigen (HBVsAg) or antibodies to hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
15. A history of other significant infection, including HIV. HIV testing is not mandatory unless clinically indicated.
16. Participants should be excluded if they have a history of allergy to study drug components, or a history of severe hypersensitivity reaction to any monoclonal antibody.
17. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol
18. Female patient is pregnant or lactating.