A Phase 1a/b Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of OMP-131R10

Study Overview
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Brief Summary
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This is an open-label Phase 1a/b dose-escalation study to assess the safety, tolerability, and PK of OMP-131R10 as a single agent for advanced solid tumors and in subjects with metastatic colorectal cancer.

Detailed Description
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The Phase 1a portion of the study in subjects with advanced solid tumors will consist of a dose escalation part followed by a dose-expansion cohort. OMP-131R10 will be administered IV on the first day of each 14-day cycle. Dose escalation will follow a traditional 3+3 framework. Treatment will be continued until progressive disease or unacceptable toxicity. The Phase 1b portion of the study will be conducted in subjects with metastatic colorectal cancer whose tumors have progressed after at least 1 line of therapy for metastatic disease. Treatment will consist of OMP-131R10 and the FOLFIRI chemotherapy regimen.

Official Title
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A Phase 1a/b Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of OMP-131R10 in Advanced Solid Tumors and in Combination With FOLFIRI for Patients With Previously Treated Metastatic Colorectal Cancer

Conditions
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Advanced Relapsed Tumors, Refractory Solid Tumors

Intervention / Treatment
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* Drug: OMP-131R10
* Drug: FOLFIRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following criteria to be eligible for the study: Phase 1a portion: Histologically confirmed advanced relapsed or refractory solid tumors that have exhausted standard of care therapy or either refuse or are not considered to be candidates for any remaining standard therapy. Age ≥18 years ECOG performance status 0 or 1 (see Appendix B) Must have evaluable disease per RECIST 1.1. (see Appendix C) Subjects must have Formalin-Fixed, Paraffin-Embedded (FFPE) tissue available either archived or fresh core or punch needle biopsied at study entry (two fresh cores/punches preferred whenever possible). Must have received their last anti-cancer therapy, including radiotherapy, chemotherapy, biologic therapy, or herbal therapy at least 3 weeks or 5 half-lives (for systemic agents), whichever is shorter, from initiation of study treatment. Platelets >100,000/mL without transfusions in the past 7 days Total bilirubin within 1.5x institutional upper limit of normal (ULN) AST (SGOT) and ALT (SGPT) <3 X institutional ULN Patients with documented liver metastases: AST (SGOT) and/or ALT (SGPT) ≤ 5 × ULN Albumin ≥ 3.0 g/dL Creatinine <1.5 X institutional ULN OR Creatinine clearance >50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal Exclusion Criteria: Subjects who meet any of the following criteria will not be eligible for participation in the study: Currently receiving any therapeutic treatment for their malignancy including other investigational agents Uncontrolled seizure disorder, active neurologic disease, or active CNS involvement except for individuals who have previously treated CNS metastases, are asymptomatic, and have no requirement for a corticosteroid dose (indicated to reduce brain edema) that is equivalent to a prednisone dose of >10mg orally per day or anti-seizure medication for at least 4 weeks prior to first dose of study drug. History of a Grade 3 or 4 allergic reaction attributed to humanized or human monoclonal antibody therapy Significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women or nursing women Subjects with congestive heart failure with New York Heart Association Classification III, or IV (see Appendix D) Known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OMP-131R10 intravenous (in the vein) infusions<br>OMP-131R10 will be administered IV on the first day of each 14-day cycle. | Drug: OMP-131R10<br>* There are 5 planned dose cohorts of OMP-131R10. Dose escalation will follow a traditional 3+3 framework. Treatment will be continued until progressive disease or unacceptable toxicity.<br>* Other names: OMP-131R10, IgG1 humanized monoclonal antibody;Drug: FOLFIRI<br>* Treatment will consist of OMP-131R10 and the FOLFIRI chemotherapy regimen.<br>|
| Experimental: FOLFIRI (5-FU, irinotecan, leucovorin).<br>dosing continues up to the 20 mg/kg dose level | Drug: OMP-131R10<br>* There are 5 planned dose cohorts of OMP-131R10. Dose escalation will follow a traditional 3+3 framework. Treatment will be continued until progressive disease or unacceptable toxicity.<br>* Other names: OMP-131R10, IgG1 humanized monoclonal antibody;Drug: FOLFIRI<br>* Treatment will consist of OMP-131R10 and the FOLFIRI 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 (DLTs) | Subject will be assessed for DLTs during the evaluation window (28 days). Once the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been determined. | DLTs during the evaluation (28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Solid Tumors and in Combination, FOLFIRI for Patients with Previously Treated Metastatic, Colorectal Cancer