MGD007 Combined With MGA012 in Relapsed/Refractory Metastatic Colorectal Cancer

NCT ID: NCT03531632

Last Updated: 2022-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-04
• Study Completion Date: 2020-02-08

Brief Summary

The primary goal of this study is to characterize the safety, tolerability, and maximum tolerated dose (MTD) of MGD007 when combined with MGA012. Pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and the anti-tumor activity of the combination of MGD007 and MGA012 will also be assessed.

Detailed Description

This study is an open-label, Phase 1b/2, dose escalation and cohort expansion study designed to characterize the safety, tolerability, PK, PD, immunogenicity, and preliminary antitumor activity of MGD007 and MGA012, administered in combination by IV infusion, in patients with histologically proven, relapsed/refractory metastatic colorectal carcinoma, irrespective of the KRAS and MMR status of their tumors.

The study consists of a Dose Escalation Phase to determine the MTD or Maximum Administered Dose (MAD; if no MTD is defined) of the combination, followed by a Cohort Expansion Phase to further define the safety and initial antitumor activity of the combination with the doses established in the Dose Escalation Phase.

Conditions

Colorectal Cancer Metastatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MGD007 + MGA012

MGD007 is a gpA33 x CD3 bi-specific DART antibody; MGA012 is an anti-PD-1 monoclonal antibody.

Group Type: EXPERIMENTAL

MGD007 + MGA012

Intervention Type: BIOLOGICAL

MGD007 and MGA012 are administered by IV infusion.

Interventions

MGD007 + MGA012

MGD007 and MGA012 are administered by IV infusion.

Intervention Type: BIOLOGICAL

Other Intervention Names

MGA012 also known as INCMGA00012

Eligibility Criteria

Inclusion Criteria

• Histologically proven, relapsed/refractory metastatic colorectal cancer
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Measurable disease per RECIST 1.1 criteria
• Participants in the Dose Escalation Phase must have had recurrence, progression or intolerance to standard therapy consisting of at least 2 prior standard regimens (containing a fluoropyrimidine plus a platinum analogue and/or irinotecan) for metastatic disease. Participants in the Cohort Expansion portion will be allowed to participate after 1 prior standard regimen. Those who are inappropriate candidates for or have refused treatment with these regimens are also eligible. No more than 5 prior therapies are permitted. Patients previously treated with MGD007 on Study Protocol CP-MGD007-01 and who did not develop antibodies to MGD007 while on the CP-MGD007-01 study, may be enrolled. Patients that were previously treated on CP-MGD007-01 will only be treated on this study once MTD/MAD has been defined.
• Availability of sufficient tumor specimens to enable retrospective determination of gpA33, CD3, PD-1, and PD-L1 expression
• 30 participants in the Cohort Expansion portion must have lesions that are accessible for paired biopsies with acceptable clinical risk in the judgment of the investigator.

Exclusion Criteria

• Symptomatic central nervous system (CNS) metastases. No concurrent treatment for the CNS disease; no progression of CNS metastases on MRI or CT for at least 14 days after last day of prior therapy for the CNS metastases; no concurrent leptomeningeal disease or cord compression
• History of known or suspected autoimmune disease with certain exceptions
• History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation.
• Major surgery, systemic anti-neoplastic therapy, or investigational therapy within 4 weeks
• Radiation therapy within 2 weeks
• Systemic corticosteroids (≥ 10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 14 days
• History of Grade 3 or greater drug-related diarrhea/colitis during treatment with checkpoint inhibitors including anti-LAG-3, anti-PD-1, anti PD-L1, or anti-CTLA-4 antibodies
• Clinically significant cardiovascular disease; gastrointestinal disorders; pulmonary compromise; viral, bacterial, or systemic fungal infections
• History of positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome
• History of hepatitis B or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MacroGenics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Yale School of Medicine

New Haven, Connecticut, United States

Moffitt Cancer Center

Tampa, Florida, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Rochester Medical Center

Rochester, New York, United States

Carolina Biooncology Institute

Huntersville, North Carolina, United States

University of Washington

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CP-MGD007-02

Identifier Type: -

Identifier Source: org_study_id