A Phase 1a/b Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of OMP-131R10

• ClinicalTrials.gov Identifier: NCT02482441
• Recruitment Status: Completed
• First Posted: June 26, 2015
• Last Update Posted: August 11, 2020
• Sponsor: OncoMed Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Mereo BioPharma ( OncoMed Pharmaceuticals, Inc. )

Tracking Information

• First Submitted Date: June 19, 2015
• First Posted Date: June 26, 2015
• Last Update Posted Date: August 11, 2020
• Actual Study Start Date: July 16, 2015
• Actual Primary Completion Date: January 26, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 23, 2015)

Incidence of dose limiting toxicities (DLTs) [ Time Frame: DLTs during the evaluation (28 days) ]

Subject will be assessed for DLTs during the evaluation window (28 days). Once the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been determined.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 1a/b Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of OMP-131R10
• Official Title: A Phase 1a/b Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of OMP-131R10 in Advanced Solid Tumors and in Combination With FOLFIRI for Patients With Previously Treated Metastatic Colorectal Cancer
• Brief Summary: This is an open-label Phase 1a/b dose-escalation study to assess the safety, tolerability, and PK of OMP-131R10 as a single agent for advanced solid tumors and in subjects with metastatic colorectal cancer.

Detailed Description

The Phase 1a portion of the study in subjects with advanced solid tumors will consist of a dose escalation part followed by a dose-expansion cohort. OMP-131R10 will be administered IV on the first day of each 14-day cycle.

Dose escalation will follow a traditional 3+3 framework. Treatment will be continued until progressive disease or unacceptable toxicity.

The Phase 1b portion of the study will be conducted in subjects with metastatic colorectal cancer whose tumors have progressed after at least 1 line of therapy for metastatic disease.

Treatment will consist of OMP-131R10 and the FOLFIRI chemotherapy regimen.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Relapsed Tumors
• Refractory Solid Tumors

Intervention

• Drug: OMP-131R10
  There are 5 planned dose cohorts of OMP-131R10. Dose escalation will follow a traditional 3+3 framework. Treatment will be continued until progressive disease or unacceptable toxicity.
  Other Name: OMP-131R10, IgG1 humanized monoclonal antibody
• Drug: FOLFIRI
  Treatment will consist of OMP-131R10 and the FOLFIRI chemotherapy regimen.

Study Arms

• Experimental: OMP-131R10 intravenous (in the vein) infusions
  OMP-131R10 will be administered IV on the first day of each 14-day cycle.
  Interventions:

  • Drug: OMP-131R10
  • Drug: FOLFIRI
• Experimental: FOLFIRI (5-FU, irinotecan, leucovorin).
  dosing continues up to the 20 mg/kg dose level
  Interventions:

  • Drug: OMP-131R10
  • Drug: FOLFIRI

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: June 23, 2015): 50
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: March 28, 2018
• Actual Primary Completion Date: January 26, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Subjects must meet all of the following criteria to be eligible for the study:

1. Phase 1a portion: Histologically confirmed advanced relapsed or refractory solid tumors that have exhausted standard of care therapy or either refuse or are not considered to be candidates for any remaining standard therapy.
2. Age ≥18 years
3. ECOG performance status 0 or 1 (see Appendix B)
4. Must have evaluable disease per RECIST 1.1. (see Appendix C)
5. Subjects must have Formalin-Fixed, Paraffin-Embedded (FFPE) tissue available either archived or fresh core or punch needle biopsied at study entry (two fresh cores/punches preferred whenever possible).
6. Must have received their last anti-cancer therapy, including radiotherapy, chemotherapy, biologic therapy, or herbal therapy at least 3 weeks or 5 half-lives (for systemic agents), whichever is shorter, from initiation of study treatment.
7. Platelets >100,000/mL without transfusions in the past 7 days

8. Total bilirubin within 1.5x institutional upper limit of normal (ULN)

   • AST (SGOT) and ALT (SGPT) <3 X institutional ULN
   • Patients with documented liver metastases: AST (SGOT) and/or ALT (SGPT) ≤ 5 × ULN
   • Albumin ≥ 3.0 g/dL
   • Creatinine <1.5 X institutional ULN OR
   • Creatinine clearance >50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal

Exclusion Criteria:

Subjects who meet any of the following criteria will not be eligible for participation in the study:

1. Currently receiving any therapeutic treatment for their malignancy including other investigational agents
2. Uncontrolled seizure disorder, active neurologic disease, or active CNS involvement except for individuals who have previously treated CNS metastases, are asymptomatic, and have no requirement for a corticosteroid dose (indicated to reduce brain edema) that is equivalent to a prednisone dose of >10mg orally per day or anti-seizure medication for at least 4 weeks prior to first dose of study drug.
3. History of a Grade 3 or 4 allergic reaction attributed to humanized or human monoclonal antibody therapy
4. Significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
5. Pregnant women or nursing women
6. Subjects with congestive heart failure with New York Heart Association Classification III, or IV (see Appendix D)
7. Known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02482441
• Other Study ID Numbers: 131R10-001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mereo BioPharma ( OncoMed Pharmaceuticals, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: OncoMed Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Mereo BioPharma
• Verification Date: August 2020