A Study of OMP-305B83 in Subjects With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to test the safety and efficacy of an experimental drug, OMP-305B83, when given in combination with FOLFIRI or FOLFOX. OMP-305B83 is a humanized bispecific monoclonal antibody and was developed to target cancer stem cells. Based on preclinical studies, it is believed that OMP-305B83 may block the growth of cancer stem cells and may also impair the productive growth of new blood vessels, which tumors need to grow and spread. The study is sponsored by OncoMed Pharmaceuticals, which is referred to as OncoMed or the Sponsor.

Detailed Description
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This is an open-label, Phase 1b dose escalation and expansion study of OMP-305B83 plus FOLFIRI or FOLFOX to evaluate the safety, efficacy, and pharmacokinetics of OMP-305B83 in combination with FOLFIRI or FOLFOX in patients with 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 5 years. Patients will be enrolled in two stages: a dose-escalation stage and an expansion phase.

Official Title
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A Phase 1b Study of OMP-305B83 Plus FOLFIRI or FOLFOX as Second Line Therapy in Subjects With Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: OMP-305B83
* Drug: FOLFIRI
* Drug: FOLFOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1 Age >21 years Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate organ and marrow function For women of childbearing potential and men with partners of childbearing potential, agreement (by patient and/or partner) to use two effective forms of contraception from study entry through at least 6 months after the termination visit. Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Receiving any other investigational agents or any other anti-cancer therapy Receiving prior hepatic intra-arterial chemotherapy Known significant clinically significant gastrointestinal disease Patients with brain metastases (treated or untreated) leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease Significant intercurrent illness that will limit the patient's ability to participate in the study or may result in their death over the next 18 months Pregnant or nursing women Inability to comply with study and follow up procedure

Ages Eligible for Study
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Minimum Age: 21 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: OMP-305B83 combined with FOLFIRI or FOLFOX<br> | Drug: OMP-305B83<br> <br> * Other names: bispecific monoclonal antibody;Drug: FOLFIRI<br>* Treatment will consist of OMP-305B83 and the FOLFIRI chemotherapy regimen.<br>Drug: FOLFOX<br>* Treatment will consist of OMP-305B83 and the FOLFOX chemotherapy regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicities | The maximum tolerated dose (MTD) or maximum administered dose (MAD) will be determined in patients treated with OMP-305B83 in combination with FOLFIRI or FOLFOX | Subjects will be treated and observed for DLT through the end of the first cycle (Days 0-28). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of OMP-305B83 in combination with FOLFIRI or FOLFOX will be assessed by adverse event monitoring, physical exams, vital signs, clinical laboratory testing, ECGs, echocardiograms, anti-OMP-305B83 testing, and subject interview on an ongoing basis. |  | Through study completion, an average of 8 months | 
| Immunogenicity (in terms of formation of anti-drug antibod(ies) against OMP-305B83 in percentage of subjects) of OMP-305B83 in combination with FOLFIRI or FOLFOX |  | Through study completion, an average of 8 months | 
| Response Rate assessed by RECIST criteria 1.1 |  | At 56 day intervals while on treatment, through study completion, an average of 8 months | 
| Response Rate assessed by tumor marker CEA |  | At 28 day intervals while on treatment, through study completion, an average of 8 months | 
| Progression Free Survival |  | Up to 5 years |