A Phase 1b Dose Escalation Study of the Safety and Pharmacodynamics of Brontictuzumab in Combination with Chemotherapy for Subjects with Previously Treated Metastatic Colorectal Cancer.

This is a phase 1b dose escalation study of the safety and pharmacodynamics of brontictuzumab in combination with chemotherapy for subjects with previously treated metastatic colorectal cancer. This study consists of a screening period, a treatment period and a post-treatment follow up period in which patients will be followed for survival for up to 24 months. Patients will be enrolled in two stages: a dose-escalation stage and an expansion phase.

Approximately 34 patients will be enrolled in this study at approximately 5 study centers in the United States.

Inclusion Criteria:

• Histologically confirmed metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if KRAS wild-type, an anti-EGFR therapy
• ECOG performance status 0 or 1

Exclusion Criteria:

• Prior treatment with gamma secretase inhibitors or other Notch 1 inhibitors

• Subjects with known active HIV infection. Subjects with HIV that are under a stable anti-retroviral regimen and have no evidence of immune deficiency (normal CD4 counts), undetectable viral load, and no HIV-related infections are eligible

• Subjects with uncontrolled diarrhea <30 days prior to first administration of study drug

• Subjects with any history of or current clinically significant gastrointestinal disease including, but not limited to:

  • Inflammatory bowel disease (including ulcerative colitis and Crohn's disease)
  • Active peptic ulcer disease
  • Known intraluminal metastatic lesion(s) with risk of bleeding