A Dose Escalation Study of OMP-52M51 in Subjects With Solid Tumors

NCT01778439 | Completed Phase 1

• 1 other identifier: 52M51-002
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open-label Phase 1a dose escalation study of single-agent OMP-52M51 in subjects with relapsed or refractory solid tumors. Study includes a dose escalation phase and expansion phase. Subjects will be assessed for safety, immunogenicity, pharmacokinetics, biomarkers, and efficacy.

Conditions

Relapsed or Refractory Solid Tumors

Keywords

Phase 1; Dose escalation; relapsed or refractory; solid tumor

Outcome Measures

Primary Outcomes (1)

• Safety profile of OMP-52M51 in subjects with relapsed or refractory solid tumors

  Subjects will be assessed for DLTs from Days 0-29. Adverse events will be reported through 30 days after the last dose

Secondary Outcomes (3)

• Pharmacokinetics (PK) of OMP-52M51 in subjects with relapsed or refractory solid tumors

  PK analyses at various time points following the 1st and 2nd doses, immediately pre and post-dose for all subsequent doses at treatment term, every 4 weeks after discontinuation of study drug or 12 weeks

• Immunogenicity

  Assessed at baseline, prior to each dose, at treatment termination and every 4 weeks after the discontinuation of the study drug for 12 weeks.

• Preliminary Efficacy

  Evaluation for response will be assessed on day 70 of study and every 8 weeks (or 9 weeks for Q3W schedule) thereafter and will be based on RECIST v1.1.

Study Arms (1)

OMP-52M51

EXPERIMENTAL

Drug: OMP-52M51

Interventions

OMP-52M51 DRUG

OMP-52M51

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following criteria to be eligible for the study:
• Age \>18 years
• ECOG performance status \<2 (see Appendix B)
• Solid tumor malignancy for which there is no remaining standard therapy or either refuse or are not considered to be candidates for any remaining standard therapy.
• Must have a tumor that is measurable or evaluable per RECIST v1.1 in the dose escalation phase. In the expansion cohort(s), subjects must have measurable disease.
• 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) for determination of Notch1 pathway activation status.
• Must have received their last chemotherapy, biologic, radiotherapy, or investigational therapy at least 4 weeks prior to enrollment; 6 weeks if the last regimen included BCNU or mitomycin C.
• Subjects must have normal organ and marrow function as defined below:
• Absolute neutrophil count \>1500/mL without growth factor support in the past 7 days
• Platelets \>100,000/mL without transfusions in the past 7 days
• Total bilirubin \<1.5 X institutional upper limit of normal (ULN) (\<2X ULN for subjects with Gilbert's syndrome)
• AST (SGOT) and ALT (SGPT) \<3 X institutional ULN (for subjects with hepatic involvement \<5 X institutional ULN but cannot be associated with elevated bilirubin)
• PT/INR and aPTT within 1.5 X institutional ULN
• Creatinine \<1.5 X institutional ULN OR
• Creatinine clearance \>60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal

You may not qualify if:

• Subjects who meet any of the following criteria will not be eligible for participation in the study:
• Currently receiving any therapeutic treatment for their malignancy including other investigational agents
• Prior treatment with gamma secretase inhibitors or other Notch 1 inhibitors
• 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 higher doses of corticosteroids (\> prednisone 10mg orally per day) or anti-seizure medication for at least 4 weeks prior to first dose of study drug.
• History of a Grade 4 allergic reaction attributed to humanized or human monoclonal antibody therapy
• 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
• Pregnant women or nursing women
• Ongoing malignancies or malignancies in remission \<3 years other than the malignancies included in this trial. Patients with history of known squamous cell skin cancers within the past 3 years will not be included in this trial. The following prior malignancies are allowable irrespective of when they occurred: in situ carcinoma of the cervix, in situ ductal breast cancer, and low-grade local bladder cancer.
• Subjects with known HIV infection
• Known bleeding disorder or coagulopathy
• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
• Hemoptysis in excess of 2.5 mL(or one-half teaspoon) within 8 weeks of first dose of study drug.
• Subjects receiving heparin, warfarin, or other similar anticoagulants, except for subjects on low molecular weight heparin for DVT/PE prophylaxis. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.
• New York Heart Association Classification II, III, or IV (see Appendix D)
• Subjects with poorly controlled blood pressure (defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) that is not responsive to medical therapy. Subjects taking antihypertensive medications must be taking ≤2 medications to obtain this level of blood pressure control.

Sponsors & Collaborators

• OncoMed Pharmaceuticals, Inc.: lead

Study Sites (6)

University of California, San Francisco/Helen Diller Cancer Institute

San Francisco, California, 94115, United States

Location

University of Colorado Denver -RCI-South Tower

Aurora, Colorado, 80045, United States

Location

Karmanos Cancer Institute (KCI)

Detroit, Michigan, 48201, United States

Location

Wayne State University/Oncology Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Ferrarotto R, Eckhardt G, Patnaik A, LoRusso P, Faoro L, Heymach JV, Kapoun AM, Xu L, Munster P. A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors. Ann Oncol. 2018 Jul 1;29(7):1561-1568. doi: 10.1093/annonc/mdy171.

  PMID: 29726923 DERIVED

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2013
• First Posted: January 29, 2013
• Study Start: February 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: August 11, 2020

Record last verified: 2020-08

Locations

US (6)