A Study of Brontictuzumab With Chemotherapy for Subjects With Previously Treated Metastatic Colorectal Cancer

A Phase 1b Dose Escalation Study of the Safety and Pharmacodynamics of Brontictuzumab in Combination With Chemotherapy for Subjects With Previously Treated Metastatic Colorectal Cancer

A Phase 1b Dose Escalation Study of the Safety and Pharmacodynamics of Brontictuzumab in Combination with Chemotherapy for Subjects with Previously Treated Metastatic Colorectal Cancer.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: brontictuzumab; Drug: trifluridine/tipiracil

Detailed Description

This is a phase 1b dose escalation study of the safety and pharmacodynamics of brontictuzumab in combination with chemotherapy for subjects with previously treated metastatic colorectal cancer. 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 24 months. Patients will be enrolled in two stages: a dose-escalation stage and an expansion phase.

Approximately 34 patients will be enrolled in this study at approximately 5 study centers in the United States.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States
      • Denver
  • Florida
    • Miami, Florida, United States
      • Miami
    • Sarasota, Florida, United States
      • Sarasota
  • South Carolina
    • Charleston, South Carolina, United States
      • Charleston
  • Tennessee
    • Nashville, Tennessee, United States
      • Nashville

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if KRAS wild-type, an anti-EGFR therapy
• ECOG performance status 0 or 1

Exclusion Criteria:

• Prior treatment with gamma secretase inhibitors or other Notch 1 inhibitors
• Subjects with known active HIV infection. Subjects with HIV that are under a stable anti-retroviral regimen and have no evidence of immune deficiency (normal CD4 counts), undetectable viral load, and no HIV-related infections are eligible
• Subjects with uncontrolled diarrhea <30 days prior to first administration of study drug

• Subjects with any history of or current clinically significant gastrointestinal disease including, but not limited to:

  • Inflammatory bowel disease (including ulcerative colitis and Crohn's disease)
  • Active peptic ulcer disease
  • Known intraluminal metastatic lesion(s) with risk of bleeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brontictuzumab and trifluridine/tipiracil; Brontictuzumab will be administered per protocol and trifluridine/tipiracil per label.	Drug: brontictuzumab; starting dose of 1.5mg/kg administered intravenously (IV); Other Names: OMP-52M51; Drug: trifluridine/tipiracil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients with adverse events	up to approximately 2 years
Percentage of patients with dose limiting toxicities	28 days
Percentage of patients with anti-brontictuzumab antibodies	up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	approximately 2 years
Progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1	approximately 2 years
Changes in number of circulating tumor cells	approximately 2 years
Overall survival	approximately 2 years

Collaborators and Investigators

• Sponsor: OncoMed Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: January 13, 2017
• First Submitted That Met QC Criteria: January 24, 2017
• First Posted (Estimate): January 25, 2017

Study Record Updates

• Last Update Posted (Actual): August 11, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Trifluridine
• Other Study ID Numbers: 52M51-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No