Primary Outcome Measures
- Number of participants with adverse events [ Time Frame: 28 days after last dose of study drug ]
adverse events, serious adverse events
Secondary Outcome Measures
- Peak plasma concentration [ Time Frame: 8 days ] PK of MGD009
- Number of participants that develop anti-drug antibodies [ Time Frame: first dose through 28 days after last dose of study drug ] Proportion of patients who develop anti-MGD0009 antibodies, immunogenicity
- Change in tumor volume [ Time Frame: Weeks 6, 15, 24, 33, 42, 51, 60, 69, 78, 87, 96, 105 ]
Anti-tumor activity of MGD006 using both conventional RECIST 1.1 and immune-related RECIST criteria.
Detailed Description
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.
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).
Eligibility
- Inclusion Criteria
- Histologically and/or cytologically proven unresectable locally advanced or metastatic tumors that express B7-H3 on the membrane or vasculature. The requirement for previous systemic therapy may be waived if a person was intolerant of standard front-line therapy
- Dose escalation phase prior systemic treatment requirements:
- mesothelioma, pancreatic cancer: 1-3 prior treatments
- urothelial, SCHNN, prostate, soft tissue sarcoma, prostate cancer, TNBC, ccRCC, NSCLC: 1-5 prior treatments
- ovarian cancer: 2-4 prior treatments
- colon cancer: 2-4 prior treatments
- melanoma: at least 1 prior treatment (including immunotherapy).
- Patients with prior immune checkpoint inhibitors must have related toxicities reduced to Grade 0, 1, or baseline
- Measurable disease per RECIST 1.1 criteria
- Easter Cooperative Oncology Group (ECOG) performance status 0 or 1
- Acceptable laboratory parameters and adequate organ reserve.
- Exclusion Criteria
- Patients with central nervous system (CNS) involvement must have been treated, be asymptomatic, do not exhibit progression of CNS metastases on MRI or CT within 28 days, and do not have concurrent leptomeningeal disease or cord compression.
- Clinically significant pulmonary compromise (e.g. require supplemental oxygen)
- History of autoimmune disease with certain exceptions such as vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic therapy within the past 2 years, patients with history of Grave’s disease that are now euthyroid clinically and by lab testing
- History of clinically-significant cardiovascular disease
- History of clinically-significant gastrointestinal (GI) disease; GI perforation within 1 year; GI bleeding or acute pancreatitis within 3 months; or diverticulitis within 4 weeks of first study drug administration
- Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days of first study drug administration
- Known history of hepatitis B or C infection or known positive test for hepatitis B surface antigen or core antigen, or hepatitis C polymerase chain reaction (PCR)
- Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome
- History of allogeneic bone marrow, stem cell, or solid organ transplant
- Treatment with systemic cancer therapy or investigational therapy within 4 weeks of first study drug administration; radiation within 2 weeks; corticosteroids (greater than or equal to 10 mg prednisone or equivalent per day) or other immune suppressive drugs within 2 weeks of first study drug administration
- Trauma or major surgery within 4 weeks of first study drug administration
- Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient contained in the drug or vehicle formulation for MGD009
