ANZUP - Non-clear Cell Post Immunotherapy CABozantinib (UNICAB)

Inclusion Criteria: * Histologically confirmed un-resectable, locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic non-clear cell renal cell histology (comprising greater than 50% of the tumour) including: 1. Papillary renal cell carcinoma (type 1) 2. Papillary renal cell carcinoma (type 2) 3. Other subtypes: including chromophobe renal cell carcinoma, sarcomatoid renal cell carcinoma, Xp11 translocation (TFE3+ IHC) carcinoma, other renal carcinoma NOS * Patient is either; 1. Ineligible for checkpoint inhibitor immunotherapy due to pre-existing autoimmune disorder in the opinion of the investigator, or 2. Has progressed following treatment with checkpoint inhibitor immunotherapy * Be greater than 18 years of age on the day of signing informed consent * At least 1 target lesion according to RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (refer to Appendix 1) * Adequate bone marrow function (performed within 14 days prior to registration and with values within the ranges specified below): 1. Haemoglobin ≥ 90g/L 2. Platelets ≥ 100x109/L 3. Neutrophil count ≥ 1.5x109/L * Adequate liver function (performed within 14 days prior to registration and with values within the ranges specified below): 1. Bilirubin ≤ 1.5 x upper limit of normal (ULN) except for participants with known Gilbert's syndrome who can have total bilirubin \< 3.0 mg/dL 2. AST or ALT ≤ 3.0 x ULN (or ≤ 5.0x ULN in the presence of liver metastases) * Adequate renal function (performed within 14 days prior to registration and with values within the ranges specified below): 1. Creatinine ≤ 1.5x ULN, or Creatinine clearance (CrCl) ≥ 30mL/min (use Cockcroft-Gault Formula, refer to Appendix 2) 2. Urinalysis (dipstick) negative for protein, or for those with positive protein detected on urinalysis (≥2+), urine protein-to-creatinine ratio (UPCR) ≤ 1mg/mg (≤ 113.2mg/mmol) * Negative pregnancy test for female participants of childbearing potential within 72 hours prior to registration. If urine test cannot be confirmed as negative, a negative serum pregnancy test is required. * Female participants of childbearing potential must be willing to use two methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for greater than 1 year. * Male participants with sexual partners of childbearing age must agree to use an adequate method of contraception, must agree to use a condom during intercourse and must agree to refrain from sperm donation starting with the first dose of study therapy through 120 days after the last dose of study therapy. * Able to provide a formalin-fixed paraffin embedded (FFPE) tumour block, representative of the participant's primary or metastatic disease (preferred), which must be forwarded to the Centre for Biostatistics and Clinical Trials (BaCT) within 10 working days post registration (if not previously collected for the UNISoN study). Note: If FFPE tumour tissue block is not obtainable, then unstained slides are also acceptable. If archival tissue is not available, patient must be willing to provide a fresh tumour biopsy. * Willing and able to start treatment within 14 days of registration, and to comply with all study requirements, including the timing and/or nature of the required treatment and assessments * Has provided signed, written informed consent. Exclusion Criteria: * Patients with urothelial or transitional cell carcinoma of the renal pelvis or ureter * 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. * 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 metastases have been shown to be stable on repeat imaging post treatment and steroid treatment has been ceased for ≥ 3 weeks. * Serious Cardiovascular disorders: 1. Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias. 2. Uncontrolled hypertension defined as sustained BP \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment. 3. Stroke (including TIA), myocardial infarction, or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before randomization. * Active infection requiring systemic therapy within 14 days before registration. * Concurrent treatment with strong CYP3A4 inducers or inhibitors (such as ketoconazole and rifampicin), P-glycoprotein substrates (such as fexofenadine, ambrisentan, dabigatran etexilate, digoxin, colchicine, maraviroc, posaconazole, ranolazine, saxagliptin, sitagliptin, talinolol and tolvaptan), MRP2 inhibitors (such as cyclosporine, efavirenz and emtricitabine), or direct oral anticoagulants such as thrombin inhibitors or factor Xa inhibitors. Use of low molecular weight heparin (LMWH) is permitted. * Life expectancy of less than 3 months. * Prior systemic therapy, surgery or radiation therapy within 4 weeks before registation. Note: If the participant has undergone major surgery, complete wound healing must have occurred 1 month prior to registration. Patients must not have received prior targeted therapy or chemotherapy, but may have received previous checkpoint immunotherapy, for example, via the UNISoN trial (NCT03177239) * History of another active malignancy 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 treated for other malignancies and have a \<5% chance of relapse according to the investigator are eligible for this study. * Other significant active infection, including hepatitis B, hepatitis C and HIV. Hepatitis and HIV testing is not mandatory unless clinically indicated. * Participants should be excluded if they have a history of allergy to study drug components or problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption * Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol * Patient is pregnant or breastfeeding.