Metastatic disease not amenable to potentially curative surgery and with available archival tumor tissue or fresh tumor tissue biopsy.
Presence of at least 1 measurable lesion assessed by CT and/or MRI according to RECIST 1.1.
For Cohort A:
- First line metastatic colorectal cancer.
For Cohort B:
- Second line metastatic colorectal cancer that has progressed on prior chemotherapy administered for metastatic disease and which must include a fluoropyrimidine and oxaliplatin.
For Cohort C:
- Second line metastatic gastroesophageal cancer that has progressed on prior line of chemotherapy administered for metastatic disease, and which must include a platinum agent and fluoropyrimidine doublet.
For Cohort D:
- Second or third line metastatic renal cell carcinoma with a clear-cell component and has received one or two lines of treatment for metastatic disease that included an anti-angiogenic agent for at least 4 weeks with radiologic progression on that treatment.
For subjects starting from Part 1a in Cohorts A and B:
Serum hs-CRP at screening ≥ 10 mg/L.
Not requiring immediate initiation of anti-cancer therapy per investigator's best judgement.
For subjects starting from Part 2 in Cohorts C and D:
- Serum hs-CRP at screening ≥ 10 mg/L.
For All Cohorts:
Currently receiving any of the prohibited medications or has contraindications as outlined in the protocol.
Symptomatic brain metastases or brain metastases that require directed therapy (such as focal radiotherapy or surgery).
Suspected or proven immunocompromised state, or infections (as defined in the protocol).
Conditions that have a high risk of clinically significant bleeding after administration of anti-VEGF agents.
Clinically significant, uncontrolled or recent (within last 6 months) cardiovascular disease.
For Cohort D:
Concomitant medications, herbal supplements, and/or fruits and their juices that are known as strong inhibitors or inducers of CYP3A4/5, and medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
Impairment of GI function or GI disease that may significantly alter the absorption of cabozantinib.
Other protocol-defined inclusion/exclusion criteria may apply