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

MacroGenics36 sites in 5 countries162 target enrollmentDecember 12, 2018

ConditionsSquamous Cell Non Small Cell Lung Cancer Prostate Cancer Metastatic Cutaneous Melanoma Colorectal Cancer Advanced Cancer Solid Tumor, Adult

InterventionsLorigerlimab

DrugsLorigerlimab

Overview

Phase: Phase 1
Intervention: Lorigerlimab
Conditions: Squamous Cell Non Small Cell Lung Cancer
Sponsor: MacroGenics
Enrollment: 162
Locations: 36
Primary Endpoint: Incidence of treatment-emergent adverse events
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of lorigerlimab.

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.

Registry

clinicaltrials.gov

Start Date

December 12, 2018

End Date

January 27, 2025

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

MacroGenics

Responsible Party

Sponsor

Eligibility Criteria

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:
•Checkpoint inhibitor-naïve squamous cell NSCLC, including:
•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
•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 therapy.
•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 (PCWG-2).
•Rising PSA defined as at least two sequential rises in PSA.

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 (this does not apply to the melanoma expansion cohort).
•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 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 administration.
•Radioligand (e.g., radium-223) within 6 months prior to initiation of study drug administration for mCRPC in the Cohort Expansion Phase.