A Study to Evaluate Ibrutinib Combination Therapy in Patients With Selected Gastrointestinal and Genitourinary Tumors

Inclusion Criteria:

- RCC (clear cell), urothelial carcinoma (transitional cell), gastric or
gastro-esophageal junctional (GEJ) adenocarcinoma, or K-RAS or N-RAS wild-type EGFR
expressing CRC

- For RCC:

- previously received at least 1 but no more than 4 lines of therapy, one therapy
must have included a VEGF TKI

- ECOG performance status of 0-1 (score of 2 may be acceptable)

- For urothelial carcinoma:

- previously received at least 1 but no more than 2 lines of therapy, one therapy
must have included a platinum based regimen

- ECOG performance status of 0-1

- For gastric or GEJ adenocarcinoma:

- previously received at least 1 but no more than 3 lines of therapy, one therapy
must have included a fluoropyrimidine based regimen

- ECOG performance status of 0-1

- For CRC:

- previously received at least 2 but no more than 4 lines of therapy, which must
have included both an irinotecan and an oxaliplatin based regimen

- ECOG performance status of 0-1 (score of 2 may be acceptable)

- For all cohorts:

- Adequate hematologic function:

- Absolute neutrophil count (ANC) >1500 cells/mm3

- For RCC, platelet count ≥80,000 cells/mm3

- For urothelial carcinoma, gastric or GEJ adenocarcinoma, and CRC, platelet
count ≥100,000 cells/mm3

- For RCC, urothelial carcinoma, and gastric or GEJ adenocarcinoma, hemoglobin
≥8.0 g/dL

- For CRC, hemoglobin ≥9.0 g/dL

- Adequate hepatic and renal function defined as:

- AST and/or ALT ≤5.0 x upper limit of normal (ULN) if liver metastases, or ≤3
x ULN without liver metastases

- Alkaline phosphatase <3.0 x ULN or ≤5.0 x ULN if liver or bone metastases
present

- Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or
of non-hepatic origin, such as hemolysis)

- Estimated Creatinine Clearance ≥30 mL/min

Exclusion Criteria:

- For RCC, prior treatment with everolimus or temsirolimus

- For urothelial carcinoma, prior treatment with any taxane

- For gastric or GEJ adenocarcinoma, prior treatment with any taxane

- For CRC, prior treatment with cetuximab or panitumumab

- For all cohorts:

- concomitant use of warfarin or other Vitamin K antagonists

- history of stroke or intracranial hemorrhage within 6 months prior to enrollment

- major surgery within 4 weeks of first dose of study drug

- requires treatment with strong CYP3A inhibitors

- known bleeding disorders or hemophilia