Inclusion Criteria: 

• 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.

Exclusion Criteria:

• 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.