Clinical Trials /

MGD007 Combined With MGA012 in Relapsed/Refractory Metastatic Colorectal Cancer

NCT03531632

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MGD007 Combined With MGA012 in Relapsed/Refractory Metastatic Colorectal Cancer
  • 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 IDs

  • ORG STUDY ID: CP-MGD007-02
  • NCT ID: NCT03531632

Conditions

  • Colorectal Cancer Metastatic

Interventions

DrugSynonymsArms
MGD007 + MGA012MGA012 also known as INCMGA00012MGD007 + MGA012

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
MGD007 + MGA012ExperimentalMGD007 is a gpA33 x CD3 bi-specific DART antibody; MGA012 is an anti-PD-1 monoclonal antibody.
  • MGD007 + MGA012

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with adverse events
Time Frame:Up to 30 days after last dose
Safety Issue:
Description:Adverse Events, Serious Adverse Events

Secondary Outcome Measures

Measure:Peak plasma concentration
Time Frame:7 weeks
Safety Issue:
Description:PK of MGD007 and MGA012 in combination
Measure:Number of participants that develop anti-drug antibodies
Time Frame:1 year
Safety Issue:
Description:Proportion of patients who develop anti-MGD007/MGA012 antibodies, immunogenicity
Measure:Change in tumor volume
Time Frame:Every 8 weeks
Safety Issue:
Description:Anti-tumor activity of MGD007+MGA012 using both conventional RECIST 1.1 and immune-related RECIST criteria.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MacroGenics

Last Updated