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

Phase 1
Terminated
Conditions
Locally Advanced Cancer
Metastatic Cancer
Interventions
Registration Number
NCT03119428
Lead Sponsor
OncoMed Pharmaceuticals, Inc.
Brief Summary

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

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).

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
33
Inclusion Criteria
  1. 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.
  2. Ability to understand the willingness and to sign a written informed consent document
  3. Age >/= 18 years
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  5. Life expectancy >/=12 weeks
  6. Measurable disease per response evaluation criteria in solid tumors.
  7. Adequate hematologic and organ function
  8. 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
  1. 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
  2. Active autoimmune disease or a history of severe autoimmune disease or syndrome
  3. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  4. Inability to comply with study and follow-up procedures.
  5. Pregnancy, lactation, or breastfeeding women.
  6. 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.
  7. Known clinically significant liver disease,
  8. 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.
  9. 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
OMP-313M32 and NivolumabOMP-313M32Intravenous (in the vein) infusions of OMP-313M32 in combination with nivolumab
OMP-313M32 and NivolumabNivolumabIntravenous (in the vein) infusions of OMP-313M32 in combination with nivolumab
OMP-313M32OMP-313M32Intravenous (in the vein) infusions of OMP-313M32 as a single agent
Primary Outcome Measures
NameTimeMethod
Incidence of dose limiting toxicities (DLTs)Subjects will be assessed for DLTs through the end of the first cycle (Days 1-29)

The Maximum tolerated dose (MTD) or maximum administered dose (MAD) will be determined in patients treated with OMP-313M32 in combination with nivolumab

Incidence of treatment emergent adverse eventsup to approximately 2 years

Percentage of patients with adverse events

Secondary Outcome Measures
NameTimeMethod
Pharmacokinetic Outcome Measures (AUC) - Phase 1a1st 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.

Area under the plasma concentration versus time curve (AUC) will be evaluated

Pharmacokinetic Outcome Measures (AUC) - Phase 1b1st 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.

Area under the plasma concentration versus time curve (AUC) will be evaluated

Pharmacokinetic Outcome Measures (T1/2) - Phase 1a1st 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.

The half life (T1/2) of OMP-313M32 will be assessed

Pharmacokinetic Outcome Measures (T1/2) - Phase 1b1st 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.

The half life (T1/2) of OMP-313M32 will be assessed

Immunogenicity of OMP-313M32up to approximately 2 years

Percentage of patients with anti-OMP-313M32 antibodies assessed

Objective Responseup to approximately 2 years

Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Progression-free survivalapproximately 2 years

Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Trial Locations

Locations (5)

Oklahoma

🇺🇸

Oklahoma City, Oklahoma, United States

Nashville

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Nashville, Tennessee, United States

Durham

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Durham, North Carolina, United States

Scottsdale

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Scottsdale, Arizona, United States

Salt Lake City

🇺🇸

Salt Lake City, Utah, United States

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