MGD007 Combined With MGA012 in Relapsed/Refractory Metastatic Colorectal Cancer

Colorectal Cancer Metastatic Clinical Trial

Official title:

A Phase 1b/2, Open Label, Dose Escalation Study of MGD007, a Humanized gpA33 × CD3 DART® Protein in Combination With MGA012, an Anti-PD-1 Antibody, in Patients With Relapsed or Refractory Metastatic Colorectal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03531632
• Other study ID #: CP-MGD007-02
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 4, 2018
• Est. completion date: February 8, 2020

Study information

• Verified date: February 2022
• Source: MacroGenics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: February 8, 2020
• Est. primary completion date: February 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer Metastatic
• Colorectal Neoplasms

Intervention

Biological:
• MGD007 + MGA012
MGD007 and MGA012 are administered by IV infusion.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Carolina Biooncology Institute	Huntersville	North Carolina
United States	Yale School of Medicine	New Haven	Connecticut
United States	University of Rochester Medical Center	Rochester	New York
United States	University of Washington	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events	Adverse Events, Serious Adverse Events	Up to approximately 12 weeks
Secondary	Peak Plasma Concentration	PK of MGD007 and MGA012 in combination	7 weeks
Secondary	Number of Participants That Develop Anti-drug Antibodies	Proportion of patients who develop anti-MGD007/MGA012 antibodies, immunogenicity	1 year
Secondary	The Number of Participants With Response Based on the Change in Tumor Volume	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and immune related RECIST criteria: number of patients with either complete response (CR) or partial response (PR) will determine the Overall Response Rate (ORR)	Every 8 weeks