MGD007 Combined With MGA012 in Relapsed/Refractory Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Colorectal Cancer Metastatic

Intervention / Treatment
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* Biological: MGD007 + MGA012


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MGD007 + MGA012<br>MGD007 is a gpA33 x CD3 bi-specific DART antibody; MGA012 is an anti-PD-1 monoclonal antibody. | Biological: MGD007 + MGA012<br>* MGD007 and MGA012 are administered by IV infusion.<br>* Other names: MGA012 also known as INCMGA00012;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Adverse Events, Serious Adverse Events | Up to approximately 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration | PK of MGD007 and MGA012 in combination | 7 weeks | 
| Number of Participants That Develop Anti-drug Antibodies | Proportion of patients who develop anti-MGD007/MGA012 antibodies, immunogenicity | 1 year | 
| 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 |