A Study of Brontictuzumab With Chemotherapy for Subjects With Previously Treated Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: brontictuzumab
* Drug: trifluridine/tipiracil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brontictuzumab and trifluridine/tipiracil<br>Brontictuzumab will be administered per protocol and trifluridine/tipiracil per label. | Drug: brontictuzumab<br>* starting dose of 1.5mg/kg administered intravenously (IV)<br>* Other names: OMP-52M51;Drug: trifluridine/tipiracil<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with adverse events |  | up to approximately 2 years | 
| Percentage of patients with dose limiting toxicities |  | 28 days | 
| Percentage of patients with anti-brontictuzumab antibodies |  | up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) |  | approximately 2 years | 
| Progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1 |  | approximately 2 years | 
| Changes in number of circulating tumor cells |  | approximately 2 years | 
| Overall survival |  | approximately 2 years |