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Squamous Cell Non Small Cell Lung CancerPhase 1NCT03761017

MGD019 DART® Protein in Unresectable/Metastatic Cancer

A Phase 1 study testing Lorigerlimab in people with Squamous Cell Non Small Cell Lung Cancer and Prostate Cancer Metastatic, run by MacroGenics at 39 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lorigerlimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
162 participants
Where
39 sitesin 5 countries
Study dates
12 Dec 2018to 27 Jan 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • 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.

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

39 sites in 5 countries.

39 sites in 5 countries

United States17 sites

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Massachusetts General Hospital

    Boston, Massachusetts, 02215

  • UPMC Hillman Cancer Center

    Camp Hill, Pennsylvania, 17011

  • UPMC Hillman Cancer Center

    Carlisle, Pennsylvania, 17015

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • UPMC Hillman Cancer Center

    Erie, Pennsylvania, 16505

  • Oncology Hematology West p.c. dba Nebraska Cancer Specialists

    Grand Island, Nebraska, 68803

  • START Midwest

    Grand Rapids, Michigan, 49546

  • UPMC Pinnacle Harrisburg

    Harrisburg, Pennsylvania, 17101

  • UPMC Pinnacle - Community Osteopathic Medical Sciences Pavilion (MSP)

    Harrisburg, Pennsylvania, 17109

  • UPMC Pinnacle - Ortenzio Cancer Center (OCC)

    Mechanicsburg, Pennsylvania, 17050

  • The Sarah Cannon Research Institute / Tennessee Oncology

    Nashville, Tennessee, 37203

  • Nebraska Cancer Specialists

    Omaha, Nebraska, 68130

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 20850

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • UPMC Hillman Cancer Center at UPMC Memorial

    York, Pennsylvania, 17408

Other trials in United States

Poland7 sites

  • University Clinical Centre, Early Clinical Trials Unit

    Gdansk, 80-214

  • Pratia MCM Krakow

    Krakow

  • Europejskie Centrum Zdrowia Otwock

    Otwock, 05-400

  • Med-Polonia Sp. z.o.o.

    Poznan, 60-693

  • LUX MED Onkologia Sp. z.o.o.

    Warsaw, 01-748

  • Narodowy Instytut Onkologii im

    Warsaw, 02-781

  • Mazovian Onkological Hospital

    Wieliszew

Other trials in Poland

Ukraine7 sites

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

    Dnipro

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

    Kharkiv

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

    Kirovohrad

  • Kyiv City Clinical Oncological Centre

    Kyiv

  • National Cancer Institute of Ukraine

    Kyiv

  • Sumy Clinical Oncological Hospital

    Sumy

  • Communal Nonprofit Enterprise "Podilsky Regional Center of Oncology"

    Vinnytsia

Other trials in Ukraine

Bulgaria5 sites

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

    Burgas, 8000

  • Multiprofile Hospital for Active Treatment-Uni Hospital

    Panagyurishte

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

    Pleven

  • Complex Oncology Center - Ruse EOOD

    Rousse, 7002

  • University Mulitprofile Hospital for Active Treatment "Sv. Ivan Rilski

    Sofia, 1431

Other trials in Bulgaria

Spain3 sites

  • ICO Badalona / Hospital Universitari Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital Ruber Internacional

    Madrid, 20834

  • Hospital Universitario La Princesa

    Madrid, 28006

Other trials in Spain

About this study

Official title: 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 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.

Being tested
Lorigerlimab
Medical subject headings
Melanoma, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LorigerlimabBiological

    Also called MGD019

    Bispecific DART protein binding PD-1 and CTLA-4

Study groups in NCT03761017
Study groupRoleWhat they receive
Cohort 1Experimental0.03 mg/kg administered IV every 3 weeks.
Receives: Biological: Lorigerlimab
Cohort 2Experimental0.1 mg/kg administered IV every 3 weeks.
Receives: Biological: Lorigerlimab
Cohort 3Experimental0.3 mg/kg administered IV every 3 weeks.
Receives: Biological: Lorigerlimab
Cohort 4Experimental1.0 mg/kg administered IV every 3 weeks.
Receives: Biological: Lorigerlimab
Cohort 5Experimental30. mg/kg administered IV every 3 weeks.
Receives: Biological: Lorigerlimab
Cohort 6Experimental6.0 mg/kg administered IV every 3 weeks.
Receives: Biological: Lorigerlimab
Cohort 7Experimental10.0 mg/kg administered IV every 3 weeks.
Receives: Biological: Lorigerlimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 30 days after last dose

Secondary outcomes (17)

  1. Cmax

    Maximum Plasma Concentration of lorigerlimab

    Measured: up to 108 weeks

  2. Tmax

    Time to reach maximum (peak) plasma concentration of lorigerlimab

    Measured: up to 108 weeks

  3. AUC

    Area Under the Plasma Concentration versus Time Curve of lorigerlimab

    Measured: up to 108 weeks

  4. Ctrough

    Trough plasma concentration of lorigerlimab

    Measured: up to 108 weeks

  5. CL

    Total body clearance of the drug from plasma of lorigerlimab

    Measured: up to 108 weeks

  6. Vss

    Apparent volume of distribution at steady state of lorigerlimab

    Measured: up to 108 weeks

  7. t1/2

    Terminal half life of lorigerlimab

    Measured: up to 108 weeks

  8. Percent of patients with anti-drug antibodies against lorigerlimab

    Immunogenicity

    Measured: up to 108 weeks

  9. Objective response rate (ORR)

    The number of participants who have a complete response (CR) or partial response (PR) to treatment. Efficacy assessed using conventional Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

    Measured: Every 12 weeks, up to 4 years

  10. Duration of Response (DoR)

    DoR is defined as the time from the date of initial response (CR or PR) to the date of first documented PD or death from any cause, whichever occurs first

    Measured: Every 12 weeks until withdrawal of consent, lost to follow up, death, or end of the study, up to 4 years

  11. Progression free survival (PFS)

    PFS is defined as the time from the first dose date to the date of first documented PD or death from any cause, whichever occurs first.

    Measured: Tumor status assessed every 12 weeks. Survival status is assessed approximately every 12 weeks after the last dose of study treatment until withdrawal of consent, lost to follow up, death, or end of the study, up to 4 years

  12. Overall survival (OS)

    OS is defined as the time from the first dose date to the date of death from any cause.

    Measured: OS status is assessed approximately every 12 weeks after the last dose of study treatment until withdrawal of consent, lost to follow up, death, or end of the study, up to 4 years

  13. Prostate specific antigen (PSA) response rate in mCRPC

    Percent of patients with 50% or more decline in PSA and confirmed 3 weeks later

    Measured: Every 3 weeks on treatment, then every 3 months up to 2 years post last treatment

  14. Best PSA percent change in mCRPC

    Best percent change in PSA from baseline

    Measured: Every 3 weeks on treatment, then every 3 months up to 2 years post last treatment

  15. Duration of PSA response

    Time from PSA response to time of PSA progression

    Measured: Every 3 weeks on treatment, then every 3 months up to 2 years post last treatment

  16. Radiographic progression-free survival (PFS) in metastatic castration-resistant prostate cancer (mCRPC)

    Time from first dose to first occurrence of radiographic progression, or death

    Measured: up to 2 years post last treatment

  17. Time to PSA progression in mCRPC

    The time from the first dose of MGD019 to the first documented PSA progression. PSA progression is defined as an increase that is ≥ 25% and ≥ 2 ng/mL the baseline or lowest value observed, and which confirmed by a second value at least 3 weeks later

    Measured: PSA is assessed every 3 weeks while on treatment, every 3 months for up to 2 years post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Dec 2018
  2. Study start12 Dec 2018
  3. Primary completion29 Aug 2024
  4. Study completion27 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
162 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03761017
Sponsor's protocol ID
CP-MGD019-01
Status last verified
Mar 2025
First submitted
29 Nov 2018
Last updated
6 Mar 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33377134

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lorigerlimab in people with Squamous Cell Non Small Cell Lung Cancer and Prostate Cancer Metastatic, run by MacroGenics at 39 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 sites in United States, Poland, Ukraine, Bulgaria, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of treatment-emergent adverse events (time frame: 30 days after last dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03761017, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2025.

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