MGD019 DART® Protein in Unresectable/Metastatic Cancer

  • Interventional
  • Recruiting
  • NCT03761017
Eligibility Details Visit Clinicaltrials.gov

A Phase 1, First-in-Human, Open-Label, Dose Escalation and Cohort Expansion Study of MGD019, a Bispecific DART® Protein Binding PD-1 and CTLA-4 in Patients With Unresectable or Metastatic Neoplasms

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.

Gender
All

Age Group
18 Years and up

Accepting Healthy Volunteers?
No

Inclusion Criteria:

         - 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: Disease-specific prior therapy requirements to be specified.

         - 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.

        Exclusion Criteria:

         - 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 compression.

         - 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, pneumonitis.

         - 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 exceptions

         - 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 administration.

         - Treatment with radiation therapy within 2 weeks prior to initiation of study drug administration.
  • Cancer
  • Solid Tumors

At a Glance

National Government IDNCT03761017

IRB#IRB18-1426

Lead SponsorMacroGenics

Lead PhysicianMark J. Ratain

Collaborator(s)N/A

EligibilityAll
18 Years and up
Recruiting