A Study of Brontictuzumab 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