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

Phase 1

Completed

• Conditions: Advanced Relapsed Tumors; Refractory Solid Tumors
• Interventions: Drug: OMP-131R10; Drug: FOLFIRI

• Registration Number: NCT02482441
• Lead Sponsor: OncoMed Pharmaceuticals, Inc.

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 Timeline

• Study First Submitted: 2015-06-19
• Study First Submitted QC: 2015-06-23
• Study First Posted: 2015-06-26
• Study Start: 2015-07-16
• Primary Completion: 2018-01-26
• Study Completion: 2018-03-28
• Status Verified: 2020-08
• Last Update Submitted: 2020-08-10
• Last Update Posted: 2020-08-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
OMP-131R10 intravenous (in the vein) infusions	OMP-131R10	OMP-131R10 will be administered IV on the first day of each 14-day cycle.
OMP-131R10 intravenous (in the vein) infusions	FOLFIRI	OMP-131R10 will be administered IV on the first day of each 14-day cycle.
FOLFIRI (5-FU, irinotecan, leucovorin).	FOLFIRI	dosing continues up to the 20 mg/kg dose level
FOLFIRI (5-FU, irinotecan, leucovorin).	OMP-131R10	dosing continues up to the 20 mg/kg dose level

Primary Outcome Measures

Name	Time	Method
Incidence of dose limiting toxicities (DLTs)	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.

Trial Locations

Locations (7)

Massachusetts General Hospital, Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

The Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

Yale; 🇺🇸 New Haven, Connecticut, United States

M.D. Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University of Colorado Hospital Anschulz Cancer Pavilion; 🇺🇸 Aurora, Colorado, United States

UCSF; 🇺🇸 San Francisco, California, United States