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
targeted therapy. ROS1 rearrangement or BRAF mutation must have progressed
following at least 1 available EGFR (including osimertinib for EGFR T790M-mutated
NSCLC), ALK, ROS1 or BRAF targeted therapy, respectively
2. Patients that have progressed during or following treatment with platinum-based
chemotherapy for advanced disease and 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
- Checkpoint inhibitor-naïve mCRPC that has progressed during or following no more than
2 prior lines of an androgen receptor antagonist or androgen synthesis inhibitor
(e.g., enzalutamide or abiraterone, respectively), if approved and available, with a
PSA value of at least 2 ng/mL and meeting at least one of the following:
- Progression in measurable disease (RECIST v1.1).
- Appearance of 2 or more new bone lesions according to Prostate Cancer Working Group 2
- Rising PSA defined as at least two sequential rises in PSA.
- Eligible patients may have received prior chemotherapy (i.e. docetaxel), and patients
with known homologous recombination (HRR) pathway gene alterations must have received
the applicable approved therapy (e.g. olaparib).
- Cutaneous melanoma that has progressed during or following systemic treatment for
unresectable, locally advanced, or metastatic disease. Patients will have received
PD-(L)1 and/or CTLA-4 pathway inhibitors where available and indicated.
- 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. Patients may undergo a fresh tumor biopsy during
the screening period if a tumor sample is not available. Patients in the mCRPC
expansion cohort with bone only disease not amenable to fresh biopsy may be eligible
in consultation with the Sponsor.
- 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 (this does not
apply to the melanoma expansion cohort).
- 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 or major surgical procedure within 4 weeks prior to initiation of
study drug administration.
- Systemic antineoplastic therapy, or investigational therapy (for all tumor types) or
androgen receptor antagonist/androgen synthesis inhibitor for mCRPC (e.g.,
enzalutamide or abiraterone, respectively) within the 4 weeks prior to initiation of
study drug administration.
- Treatment with radiation therapy within 2 weeks prior to initiation of study drug
- Radioligand (e.g., radium-223) within 6 months prior to initiation of study drug
administration for mCRPC in the Cohort Expansion Phase.
- Serum testosterone > 50 ng/dl or > 1.7 nmol/L for mCRPC in the Cohort Expansion Phase.
- Confirmed or presumed COVID-19/SARS-CoV-2 infection. While SARS-CoV-2 testing is not
mandatory for study entry, testing should follow local clinical practice
guidelines/standards. Patients with a positive test result for SARS-CoV-2 infection,
known asymptomatic infection, or presumed infection are excluded. Patients may be
considered eligible after a resolved SARS-CoV-2 infection once he or she remains
afebrile for at least 72 hours and after other SARS-CoV-2-related symptoms have fully
recovered to baseline for a minimum of 72 hours