A Study of OMP-313M32 in Subjects With Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of OMP-31M32 as a single agent or in combination with nivolumab. OMP-313M32 is an experimental anti-TIGIT antibody that was developed to block TIGIT from binding PVR allowing the body's T-cells to destroy cancer cells.

Detailed Description
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This is an open-label, Phase 1a/b dose escalation study of OMP-31M32 administered as a single agent or in combination with nivolumab to evaluate the safety, tolerability pharmacokinetics, and pharmacodynamics in patients with locally advanced or metastatic solid tumors. 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 2 years. Subjects will be enrolled in two stages in the Phase 1a (dose escalation and expansion) and one stage in the Phase 1b (dose escalation).

Official Title
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A Phase 1a/b Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of OMP-313M32 Administered as a Single Agent or in Combination With Nivolumab to Subjects With Locally Advanced or Metastatic Solid Tumors

Conditions
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Locally Advanced Cancer, Metastatic Cancer

Intervention / Treatment
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* Drug: OMP-313M32
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic documentation of locally advanced, recurrent or metastatic solid malignancy that has progressed and standard therapy has been ineffective or intolerable. Phase 1b subjects must also have experienced disease progression after treatment with an anti PD-1 or PDL-1 agent. Ability to understand the willingness and to sign a written informed consent document Age >/= 18 years Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Life expectancy >/=12 weeks Measurable disease per response evaluation criteria in solid tumors. Adequate hematologic and organ 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. Exclusion Criteria: Anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks or 5 half lives, whichever is shorter, prior to initiation of study treatment Active autoimmune disease or a history of severe autoimmune disease or syndrome History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. Inability to comply with study and follow-up procedures. Pregnancy, lactation, or breastfeeding women. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina. Known clinically significant liver disease, Major surgical procedure within 28 days prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.

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-313M32<br>Intravenous (in the vein) infusions of OMP-313M32 as a single agent | Drug: OMP-313M32<br>* OMP-313M32 is a monoclonal antibody which binds to the human TIGIT receptor on T cells.<br>* Other names: Anti-TIGIT monoclonal antibody;|
| Experimental: OMP-313M32 and Nivolumab<br>Intravenous (in the vein) infusions of OMP-313M32 in combination with nivolumab | Drug: OMP-313M32<br>* OMP-313M32 is a monoclonal antibody which binds to the human TIGIT receptor on T cells.<br>* Other names: Anti-TIGIT monoclonal antibody;Drug: Nivolumab<br>* Human IgG4 anti-PD-1 monoclonal antibody<br>* Other names: Opdivo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicities (DLTs) | The Maximum tolerated dose (MTD) or maximum administered dose (MAD) will be determined in patients treated with OMP-313M32 in combination with nivolumab | Subjects will be assessed for DLTs through the end of the first cycle (Days 1-29) | 
| Incidence of treatment emergent adverse events | Percentage of patients with adverse events | up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Outcome Measures (AUC) - Phase 1a | Area under the plasma concentration versus time curve (AUC) will be evaluated | 1st dose and 4th dose: pre-dose, post-infusion, and 1, 3, 7 and 10 days. All other doses: pre-dose, 15 minutes and 7 days post-infusion. PK sample will be taken at treatment termination and every 4 wks for 12 wks. | 
| Pharmacokinetic Outcome Measures (AUC) - Phase 1b | Area under the plasma concentration versus time curve (AUC) will be evaluated | 1st dose and 4th dose: pre-dose and 15 minutes post-infusion. All other doses: pre-dose. PK sample will be taken at treatment termination and every 4 wks for 12 wks. | 
| Pharmacokinetic Outcome Measures (T1/2) - Phase 1a | The half life (T1/2) of OMP-313M32 will be assessed | 1st dose and 4th dose: pre-dose, post-infusion, and 1, 3, 7 and 10 days. All other doses: pre-dose, 15 minutes and 7 days post-infusion. PK sample will be taken at treatment termination and every 4 wks for 12 wks. | 
| Pharmacokinetic Outcome Measures (T1/2) - Phase 1b | The half life (T1/2) of OMP-313M32 will be assessed | 1st dose and 4th dose: pre-dose and 15 minutes post-infusion. All other doses, pre-dose.PK sample will be taken at treatment termination and every 4 wks for 12 wks. | 
| Immunogenicity of OMP-313M32 | Percentage of patients with anti-OMP-313M32 antibodies assessed | up to approximately 2 years | 
| Objective Response | Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | up to approximately 2 years | 
| Progression-free survival | Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | approximately 2 years |