The purpose of this study is to evaluate the safety of MGD009 when given to patients with B7-H3-expressing tumors. The study will also evaluate what is the highest dose of MGD009 that can be given safely. Assessments will be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics (PD) and to evaluate potential anti-tumor activity of MGD009.
This study is a Phase 1 open-label, dose escalation, cohort expansion, and efficacy follow-up study of MGD009 administered intravenously (IV) on an every-other-week schedule for up to one year (14 cycles). The dose escalation phase is designed to characterize the safety and tolerability of MGD009 and to define the maximum tolerated or maximum administered dose (MTD/MAD). This phase will enroll patients with mesothelioma, bladder cancer, melanoma, squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (ccRCC), ovarian cancer, thyroid cancer, triple-negative breast cancer (TNBC), pancreatic cancer, colon cancer, soft tissue sarcoma, or prostate cancer. In the cohort expansion phase, 6 cohorts of 16 patients each will be enrolled to further evaluate the safety and potential efficacy of MGD009 administered at the MTD/MAD dose in patients with mesothelioma, bladder cancer, melanoma, SCCHN, NSCLC, or other specific tumors that express high levels of B7-H3. Pre- and on-study biopsies are required for melanoma patients in the cohort expansion phase. Two additional cohorts (up to15 patients each) will evaluate the use of prophylaxis therapies to mitigate toxicity. The survival follow-up phase consists of the 2-year period after the final dose of study drug. All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid Tumors (RECIST) and immune-related response criteria (irRC).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
67
B7-H3 x CD3 DART protein
UCLA
Los Angeles, California, United States
Stanford University School of Medicine
Palo Alto, California, United States
University of California - San Francisco
San Francisco, California, United States
Georgetown University
Washington D.C., District of Columbia, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
New York University
New York, New York, United States
Columbia University Medical Center
New York, New York, United States
Carolina BioOncology Institute
Huntersville, North Carolina, United States
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, United States
...and 10 more locations
Number of participants with adverse events
adverse events, serious adverse events
Time frame: 28 days after last dose of study drug
Peak plasma concentration
PK of MGD009
Time frame: 8 days
Number of participants that develop anti-drug antibodies
Proportion of patients who develop anti-MGD0009 antibodies, immunogenicity
Time frame: first dose through 28 days after last dose of study drug
Change in tumor volume
Anti-tumor activity of MGD009 using both conventional RECIST 1.1 and immune-related RECIST criteria.
Time frame: Weeks 6, 15, 24, 33, 42, 51, 60, 69, 78, 87, 96, 105
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