Clinical trial NCT03119428: A Study of OMP-313M32 in Subjects With Locally Advanced or Metastatic Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Locally Advanced Cancer
Metastatic Cancer
Lead sponsor: Mereo BioPharma
Sponsor class: INDUSTRY
First posted: 2017-04-18
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility 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.

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs)
timeFrame: Subjects will be assessed for DLTs through the end of the first cycle (Days 1-29)
measure: Incidence of treatment emergent adverse events
timeFrame: up to approximately 2 years
Secondary outcomes:
measure: Pharmacokinetic Outcome Measures (AUC) - Phase 1a
timeFrame: 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.
measure: Pharmacokinetic Outcome Measures (AUC) - Phase 1b
timeFrame: 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.
measure: Pharmacokinetic Outcome Measures (T1/2) - Phase 1a
timeFrame: 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.
measure: Pharmacokinetic Outcome Measures (T1/2) - Phase 1b
timeFrame: 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.
measure: Immunogenicity of OMP-313M32
timeFrame: up to approximately 2 years
measure: Objective Response
timeFrame: up to approximately 2 years
measure: Progression-free survival
timeFrame: approximately 2 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale
state: Arizona
city: Durham
country: United States
facility: Durham
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma
state: Oklahoma
city: Nashville
country: United States
facility: Nashville
state: Tennessee
city: Salt Lake City
country: United States
facility: Salt Lake City
state: Utah
Study officials:
affiliation: Mereo BioPharma
name: John Lewicki, PhD
role: STUDY_DIRECTOR
References:
citation: 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.