MGD019 DART® Protein in Unresectable/Metastatic Cancer

NCT03761017 | Completed Phase 1 FDA Drug

• 1 other identifier: CP-MGD019-01
• Study Type: interventional
• Target: 162
• Locations: 5 countries
• Sites: 39

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events

  Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.

  30 days after last dose

Secondary Outcomes (17)

• Cmax

  up to 108 weeks

• Tmax

  up to 108 weeks

• AUC

  up to 108 weeks

• Ctrough

  up to 108 weeks

• CL

  up to 108 weeks

Study Arms (7)

Cohort 1

EXPERIMENTAL

0.03 mg/kg administered IV every 3 weeks.

Biological: Lorigerlimab

Cohort 2

EXPERIMENTAL

0.1 mg/kg administered IV every 3 weeks.

Biological: Lorigerlimab

Cohort 3

EXPERIMENTAL

0.3 mg/kg administered IV every 3 weeks.

Biological: Lorigerlimab

Cohort 4

EXPERIMENTAL

1.0 mg/kg administered IV every 3 weeks.

Biological: Lorigerlimab

Cohort 5

EXPERIMENTAL

30\. mg/kg administered IV every 3 weeks.

Biological: Lorigerlimab

Cohort 6

EXPERIMENTAL

6.0 mg/kg administered IV every 3 weeks.

Biological: Lorigerlimab

Cohort 7

EXPERIMENTAL

10.0 mg/kg administered IV every 3 weeks.

Biological: Lorigerlimab

Interventions

Lorigerlimab BIOLOGICAL

Bispecific DART protein binding PD-1 and CTLA-4

Also known as: MGD019

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6; Cohort 7

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• MacroGenics: lead

Study Sites (39)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Oncology Hematology West p.c. dba Nebraska Cancer Specialists

Grand Island, Nebraska, 68803, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

UPMC Hillman Cancer Center

Camp Hill, Pennsylvania, 17011, United States

Location

UPMC Hillman Cancer Center

Carlisle, Pennsylvania, 17015, United States

Location

UPMC Hillman Cancer Center

Erie, Pennsylvania, 16505, United States

Location

UPMC Pinnacle Harrisburg

Harrisburg, Pennsylvania, 17101, United States

Location

UPMC Pinnacle - Community Osteopathic Medical Sciences Pavilion (MSP)

Harrisburg, Pennsylvania, 17109, United States

Location

UPMC Pinnacle - Ortenzio Cancer Center (OCC)

Mechanicsburg, Pennsylvania, 17050, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 20850, United States

Location

UPMC Hillman Cancer Center at UPMC Memorial

York, Pennsylvania, 17408, United States

Location

The Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Complex Oncology Center - Burgas" EOOD, Department of Medical Oncology

Burgas, 8000, Bulgaria

Location

Multiprofile Hospital for Active Treatment-Uni Hospital

Panagyurishte, Bulgaria

Location

Multiprofile Hospital for Active Treatment "Heart and Brain"" EAD, Clinic of Medical Oncology

Pleven, Bulgaria

Location

Complex Oncology Center - Ruse EOOD

Rousse, 7002, Bulgaria

Location

University Mulitprofile Hospital for Active Treatment "Sv. Ivan Rilski

Sofia, 1431, Bulgaria

Location

University Clinical Centre, Early Clinical Trials Unit

Gdansk, 80-214, Poland

Location

Pratia MCM Krakow

Krakow, Poland

Location

Europejskie Centrum Zdrowia Otwock

Otwock, 05-400, Poland

Location

Med-Polonia Sp. z.o.o.

Poznan, 60-693, Poland

Location

LUX MED Onkologia Sp. z.o.o.

Warsaw, 01-748, Poland

Location

Narodowy Instytut Onkologii im

Warsaw, 02-781, Poland

Location

Mazovian Onkological Hospital

Wieliszew, Poland

Location

ICO Badalona / Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Ruber Internacional

Madrid, 20834, Spain

Location

Hospital Universitario La Princesa

Madrid, 28006, Spain

Location

Communal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro

Dnipro, Ukraine

Location

Communal Non-Profit Enterprise "Regional Center of Oncology", Oncosurgical Department of Head and Neck

Kharkiv, Ukraine

Location

Communal Nonprofit Enterprise "Regional Clinical Oncology Center of Kirovohrad Regional Council"

Kirovohrad, Ukraine

Location

Kyiv City Clinical Oncological Centre

Kyiv, Ukraine

Location

National Cancer Institute of Ukraine

Kyiv, Ukraine

Location

Sumy Clinical Oncological Hospital

Sumy, Ukraine

Location

Communal Nonprofit Enterprise "Podilsky Regional Center of Oncology"

Vinnytsia, Ukraine

Location

Related Publications (1)

• Berezhnoy A, Sumrow BJ, Stahl K, Shah K, Liu D, Li J, Hao SS, De Costa A, Kaul S, Bendell J, Cote GM, Luke JJ, Sanborn RE, Sharma MR, Chen F, Li H, Diedrich G, Bonvini E, Moore PA. Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule. Cell Rep Med. 2020 Dec 22;1(9):100163. doi: 10.1016/j.xcrm.2020.100163. eCollection 2020 Dec 22.

  PMID: 33377134 BACKGROUND

Related Links

• Link to published 2020 manuscript

MeSH Terms

Conditions

Melanoma; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Denise Casey, MD

  MacroGenics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2018
• First Posted: December 3, 2018
• Study Start: December 12, 2018
• Primary Completion: August 29, 2024
• Study Completion: January 27, 2025
• Last Updated: March 6, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

UA (7); BU (5); US (17); PL (7); ES (3)