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

• ClinicalTrials.gov Identifier: NCT03119428
• Recruitment Status: Terminated
• First Posted: April 18, 2017
• Last Update Posted: September 19, 2019
• Sponsor: OncoMed Pharmaceuticals, Inc.
• Information provided by (Responsible Party): OncoMed Pharmaceuticals, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Locally Advanced Cancer; Metastatic Cancer	Drug: OMP-313M32; Drug: Nivolumab	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 2, 2017
• Actual Primary Completion Date: May 15, 2019
• Actual Study Completion Date: May 15, 2019

Arms and Interventions

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 Name: 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 Name: Anti-TIGIT monoclonal antibody; Drug: Nivolumab; Human IgG4 anti-PD-1 monoclonal antibody; Other Name: Opdivo

Outcome Measures

Primary Outcome Measures :

1. Incidence of dose limiting toxicities (DLTs) [ Time Frame: 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
2. Incidence of treatment emergent adverse events [ Time Frame: up to approximately 2 years ]
   Percentage of patients with adverse events

Secondary Outcome Measures :

1. Pharmacokinetic Outcome Measures (AUC) - Phase 1a [ Time Frame: 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. ]
   Area under the plasma concentration versus time curve (AUC) will be evaluated
2. Pharmacokinetic Outcome Measures (AUC) - Phase 1b [ Time Frame: 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. ]
   Area under the plasma concentration versus time curve (AUC) will be evaluated
3. Pharmacokinetic Outcome Measures (T1/2) - Phase 1a [ Time Frame: 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. ]
   The half life (T1/2) of OMP-313M32 will be assessed
4. Pharmacokinetic Outcome Measures (T1/2) - Phase 1b [ Time Frame: 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. ]
   The half life (T1/2) of OMP-313M32 will be assessed
5. Immunogenicity of OMP-313M32 [ Time Frame: up to approximately 2 years ]
   Percentage of patients with anti-OMP-313M32 antibodies assessed
6. Objective Response [ Time Frame: up to approximately 2 years ]
   Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
7. Progression-free survival [ Time Frame: approximately 2 years ]
   Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Scottsdale

Scottsdale, Arizona, United States, 85258

United States, North Carolina

Durham

Durham, North Carolina, United States, 27710

United States, Oklahoma

Oklahoma

Oklahoma City, Oklahoma, United States, 73104

United States, Tennessee

Nashville

Nashville, Tennessee, United States, 37203

United States, Utah

Salt Lake City

Salt Lake City, Utah, United States, 84112

Sponsors and Collaborators

OncoMed Pharmaceuticals, Inc.

More Information

• Responsible Party: OncoMed Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03119428
• Other Study ID Numbers: 313M32-001
• First Posted: April 18, 2017
• Last Update Posted: September 19, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents