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

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

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Cancer; Locally Advanced Cancer
• Intervention / Treatment: Drug: OMP-313M32; Drug: Nivolumab

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).

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Durham
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Nashville
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Salt Lake City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OMP-313M32; Intravenous (in the vein) infusions of OMP-313M32 as a single agent	Drug: OMP-313M32; OMP-313M32 is a monoclonal antibody which binds to the human TIGIT receptor on T cells.; Other Names: Anti-TIGIT monoclonal antibody
Experimental: OMP-313M32 and Nivolumab; Intravenous (in the vein) infusions of OMP-313M32 in combination with nivolumab	Drug: OMP-313M32; OMP-313M32 is a monoclonal antibody which binds to the human TIGIT receptor on T cells.; Other Names: Anti-TIGIT monoclonal antibody; Drug: Nivolumab; Human IgG4 anti-PD-1 monoclonal antibody; Other Names: Opdivo

What is the study measuring?

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
Objective Response	Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	up to approximately 2 years
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
Progression-free survival	Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	approximately 2 years

Collaborators and Investigators

• Sponsor: OncoMed Pharmaceuticals, Inc.
• Investigators: Study Director: John Lewicki, PhD, Mereo BioPharma

Publications and helpful links

General Publications

• Mettu NB, Ulahannan SV, Bendell JC, Garrido-Laguna I, Strickler JH, Moore KN, Stagg R, Kapoun AM, Faoro L, Sharma S. A Phase 1a/b Open-Label, Dose-Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors. Clin Cancer Res. 2022 Mar 1;28(5):882-892. doi: 10.1158/1078-0432.CCR-21-2780.

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2017
• Primary Completion (Actual): May 15, 2019
• Study Completion (Actual): May 15, 2019

Study Registration Dates

• First Submitted: March 29, 2017
• First Submitted That Met QC Criteria: April 17, 2017
• First Posted (Actual): April 18, 2017

Study Record Updates

• Last Update Posted (Actual): August 11, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: 313M32-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No