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Clinical Trial 19615

Cancer Type: Gastrointestinal Tumor
Interventions:MGA012; MGD007

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • Richard Kim

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

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

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.

Objective

3.1.1 Primary Objectives: To characterize the safety, tolerability, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD) of MGD007 when combined with MGA012 in patients with relapsed/refractory metastatic colorectal carcinoma after at least 2 and up to 5 prior standard regimens of therapy in metastatic setting; or who did not tolerate fluoropyrimidines, oxaliplatin or irinotecan; or who are not good candidates for standard of care. 3.1.2 Secondary Objectives: To characterize the pharmacokinetics (PK), pharmacodynamic activity, and immunogenicity of MGD007 and MGA012 in combination. To investigate the preliminary antitumor activity of MGD007 combined with MGA012 as measured by objective response rate, disease control rate, and progression-free survival (PFS) rate at 16 weeks in patients with relapsed/refractory metastatic colorectal carcinoma using both conventional Response Evaluation Criteria in Solid Tumors (RECIST 1.1), Appendix 6, and immune-related response criteria (irRECIST), Appendix 7. 3.1.3 Exploratory Objectives: To explore the relationships between PK, pharmacodynamics of MGD007/MGA012, and antitumor activity. To explore the impact of this combination on PFS, immune-related PFS (irPFS), and overall survival (OS) in patients with relapsed/refractory metastatic colorectal carcinoma. To investigate the immunoregulatory activity of MGD007 combined with MGA012 in vivo, including various measures of T cell function in peripheral blood and/or tumor biopsy specimens. To assess potential biomarkers predictive of efficacy including but not limited to glycoprotein A33 (gpA33), CD3, TILs, PD-1, PD-L1, and immunosuppressive myeloid/lymphoid cells via immunohistochemistry and gene expression in archival tissue. 3.2 Cohort Expansion Phase 3.2.1 Primary Objective: To investigate antitumor activity of MGD007 combined with MGA012 when dosed at the MTD (or maximum administered dose [MAD] if no MTD is defined) as measured by objective response rate, disease control rate and PFS rate at 16 weeks in patients with relapsed/refractory metastatic colorectal carcinoma using both conventional Response Evaluation Criteria in Solid Tumors (RECIST 1.1), Appendix 6, and immune-related response criteria (irRECIST), Appendix 7. 3.2.2 Secondary Objectives: To further characterize the safety and tolerability of MGD007 when combined with MGA012 in patients with relapsed/refractory metastatic colorectal carcinoma after at least 2 lines of therapy in a metastatic setting. To characterize the PK, pharmacodynamic activity, and immunogenicity of MGD007 and MGA012 in combination. To explore the impact of this combination on PFS, immune-related PFS (irPFS), and overall survival (OS) in patients with relapsed/refractory metastatic colorectal carcinoma. 3.2.3 Exploratory Objectives: To explore the relationships between PK and pharmacodynamics of MGD007/MGA012 and antitumor activity. To investigate the immunoregulatory activity of MGD007 combined with MGA012 in vivo, including various measures of T cell function in peripheral blood and/or tumor biopsy specimens. To assess potential biomarkers predictive of efficacy including but not limited to glycoprotein A33 (gpA33), CD3, TILs, PD-1, PD-L1, and immunosuppressive myeloid/lymphoid cells via immunohistochemistry and gene expression in archival tissue and assess the effect of the combination on tumor biomarkers, comparing initial and on treatment paired tumor biopsies.

Inclusion Criteria

  • Histologically proven, relapsed/refractory metastatic colorectal cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
  • 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.
  • 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
  • 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.