The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK)
pharmacodynamics and preliminary antitumor activity of MGD019.
This Phase 1, open-label study will characterize safety, dose-limiting toxicities (DLTs), and
maximum tolerated/administered dose (MTD/MAD) of MGD019. Dose escalation will occur in a
3+3+3 design in patients with advanced solid tumors of any histology. Once the MTD/MAD is
determined, a Cohort Expansion Phase will be enrolled to further characterize safety and
initial anti-tumor activity in patients with specific tumor types anticipated to be sensitive
to dual checkpoint blockade.
- Dose escalation: Patients with histologically proven, unresectable, locally advanced
or metastatic solid tumors for whom no approved therapy with demonstrated clinical
benefit is available or patients who are intolerant to standard therapy.
- Cohort Expansion Phase:
- Checkpoint inhibitor-naïve squamous cell NSCLC, including:
1. Patients that have progressed during or following treatment with platinum-based
chemotherapy for advanced disease. Patients harboring an activating epidermal
growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK)
rearrangement must have progressed following at least one available EGFR or ALK
2. Patients with previously untreated squamous cell NSCLC without activating
mutations for whom checkpoint inhibitor therapy is not approved or available.
- Advanced non-microsatellite instability-high colorectal cancer (CRC) with recurrence,
progression, or intolerance to standard therapy consisting of at least 2 prior
standard regimens. CRC harboring an activating EGFR mutation must have progressed
during or following at least one available EGFR targeted therapy. Patients who are
inappropriate candidates for or have refused treatment with these regimens are also
eligible. Patients should have received no more than 4 prior lines of systemic
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Life expectancy ≥ 12 weeks.
- Measurable disease as per RECIST 1.1 for the purpose of response assessment must
either (a) not reside in a field that has been subjected to prior radiotherapy or (b)
have demonstrated clear evidence of radiographic progression since the completion of
prior radiotherapy and prior to study enrollment.
- All patients must have an identified formalin-fixed, paraffin embedded (FFPE) tumor
specimen (up to 20 slides or a block) for immunohistochemical evaluation of
pharmacodynamic markers of interest.
- Acceptable laboratory parameters and adequate organ reserve.
- In patients who have previously received an immune checkpoint inhibitor (e.g.,
anti-PD-L1, anti-PD-1, anti-CTLA-4), toxicities related to the checkpoint inhibitor
must have resolved to ≤ Grade 1 or baseline. Patients with well controlled immune
endocrinopathies secondary to prior checkpoint therapy are eligible.
- Patients with symptomatic CNS metastases. Patients with history of prior CNS
metastasis must have been treated, must be asymptomatic, and must not have concurrent
treatment for the CNS disease, progression of CNS metastases on magnetic resonance
imaging (MRI) or computed tomography (CT) for at least 14 days after last day of prior
therapy for the CNS metastases, or concurrent leptomeningeal disease or cord
- Patients who sustained the following Grade 3 immune checkpoint inhibitor related AEs
are ineligible: Ocular AE, changes in liver function tests that met the criteria for
Hy's law (> 3 × ULN of either ALT or AST with concurrent > 2 × ULN of total bilirubin
and without alternate etiology), neurologic toxicity, colitis, renal toxicity,
- Patients who have received prior therapy with a combination of monoclonal antibodies
against PD-1/PD-L1 and CTLA-4 will be excluded in the Cohort Expansion.
- Patients with any history of known or suspected autoimmune disease with certain
- History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation.
- History of trauma, major surgical procedure, systemic antineoplastic therapy, or
investigational therapy within the 4 weeks prior to initiation of study drug
- Treatment with radiation therapy within 2 weeks prior to initiation of study drug