A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal And Genitourinary Tumors

Condition: Metastatic Renal Cell Carcinoma, Advanced Urothelial Carcinoma, Advanced Gastric Adenocarcinoma, Metastatic Colorectal Adenocarcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02599324

Sponsor: Pharmacyclics LLC.

Phase: Phase 1/Phase 2


  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • RCC (clear cell), urothelial carcinoma (UC) (transitional cell), gastric or gastro-esophageal junctional (GEJ) adenocarcinoma, or K-RAS or N-RAS wild-type EGFR expressing CRC
  • For cohort 1 RCC: minimum of 1 and maximum of 4 prior regimens, one or more of which must have included a VEGF-TKI
  • For UC cohort 2: minimum of 1 and maximum of 2 prior regimens, one of which must have included a platinum-based regimen
  • For UC cohort 5: Minimum of 1 and maximum of 2 prior regimens, one of which must have included a checkpoint inhibitor.
  • For UC cohort 6:
  • Locally advanced or mUC who are not eligible for cisplatin chemo with a PDL-1 score (CPS) of ≥ 10 without prior treatment.
  • Locally advanced or mUC who have progressed on platinum chemo or within 12 months of neo- or adjuvant therapy with a platinum chemotherapy. A minimum of 1 and maximum of 2 prior therapies.
  • For cohort 3 gastric or GEJ adenocarcinoma: minimum of 1 and maximum of 3 prior regimens one of which must have included a fluoropyrimidine regimen
  • For cohort 4 CRC: minimum of 2 and maximum of 4 prior regimens, which must have included both an irinotecan and an oxaliplatin based regimen unless unable to tolerate irinotecan chemotherapy Laboratory:
  • Adequate hematologic function:
  • Absolute neutrophil count ≥1500 cells/mm3 (1.5 x 109/L)
  • Platelet count >80,000 cells/mm3 (80 x 109/L) for cohort 1 (RCC)
  • Platelet counts >100,000 cells/mm3 (100 x 109/L) for all UC cohorts
  • Hemoglobin ≥8.0 g/dL. for cohort 1 (RCC),all UC cohorts, and cohort 3 (GC)
  • Hemoglobin ≥9.0 g/dL for cohort 4 (CRC)
  • Adequate hepatic and renal function defined as:
  • Serum aspartate transaminase (AST) and/or alanine transaminase (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) with the exception of subjects in the GC cohort where
  • docetaxel is administered, these subjects must have bilirubin within normal limits (WNL)
  • Estimated Creatinine Clearance ≥30 mL/min (Cockcroft-Gault)

Exclusion Criteria:

  • Prior treatment with:
  • Everolimus or temsirolimus (RCC cohort 1)
  • Any taxane (UC cohort of ibrutinib + paclitaxel) (cohort 2)
  • Checkpoint inhibitors (UC cohort 6)
  • Any taxane (GC cohort 3)
  • Cetuximab or panitumumab (CRC cohort 4)
  • 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
  • UC cohort 6 only:
  • Subjects who have an active, known or suspected autoimmune disease.
  • Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.
  • Non-steroid immunosuppressive medications within 14 days before the first dose of ibrutinib and pembrolizumab.
  • Subjects in whom prior anti PD-1 / anti-PD-L1 therapy was intolerable and required discontinuation of treatment.

View trial on ClinicalTrials.gov