A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms

A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of MGD013, A Bispecific DART® Protein Binding PD-1 and LAG-3 in Patients With Unresectable or Metastatic Neoplasms

Sponsors

Lead Sponsor: MacroGenics

Source MacroGenics
Brief Summary

The primary goal of this Phase 1 study is to characterize the safety and tolerability of MGD013 and establish the maximum tolerated dose (MTD) of MGD013. Pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and the anti-tumor activity of MGD013 will also be assessed.

Detailed Description

This is a Phase 1, open-label, dose escalation and cohort expansion study designed to characterize the safety, tolerability, PK, PD, immunogenicity, and preliminary antitumor activity of MGD013 administered by IV infusion every 2 weeks. The study consists of a Dose Escalation Phase to determine the MTD or maximum administered dose (MAD) of MGD013 if no MTD is defined, followed by a Cohort Expansion Phase to further define the safety and initial antitumor activity of MGD013 with the dose established in the Dose Escalation Phase. In the Dose Escalation Phase, MGD013 will be evaluated in sequential escalating flat doses in successive cohorts of 1 to 6 patients each. Upon completion of the Dose Escalation Phase, a Cohort Expansion Phase will be initiated at the MTD/MAD. Patients with unresectable, locally advanced or metastatic solid tumors of any histology will be enrolled in the Dose Escalation Phase. The Cohort Expansion Phase will be limited to selected cohorts of patients with unresectable, locally advanced or metastatic solid tumors or hematologic malignancies for whom there is no available therapy likely to confer clinical benefit. Two additional cohorts will enroll patients with gastric/gastroesophageal cancer or epithelial ovarian cancer, with MGD013 given every 3 weeks. A separate cohort will evaluate the combination of MGD013 with margetuximab (anti-HER2 monoclonal antibody) in approximately 99 patients, in subgroups with HER2-positive gastric or gastroesophageal cancer, HER2-positive breast cancer, and any other HER2-positive cancer.

Overall Status Active, not recruiting
Start Date 2017-08-18
Completion Date 2022-07-01
Primary Completion Date 2022-05-01
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (MGD013 monotherapy) 24 months
Maximum Tolerated Dose 24 months
Secondary Outcome
Measure Time Frame
Area Under the Plasma Concentration versus Time Curve (AUC) of MGD013 and MGD013 plus margetuximab 24 months
Maximum Plasma Concentration (Cmax) of MGD013 and MGD013 plus margetuximab 24 months
Time to reach maximum (peak) plasma concentration (Tmax) of MGD013 and MGD013 plus margetuximab 24 months
Trough plasma concentration (Ctrough) of MGD013 and MGD013 plus margetuximab 24 months
Total body clearance of the drug from plasma (CL) of MGD013 and MGD013 plus margetuximab 24 months
Apparent volume of distribution at steady state (Vss) of MGD013 and MGD013 plus margetuximab 24 months
Terminal half-life (t1/2) of MGD013 and MGD013 plus margetuximab 24 months
Percent of patients with anti-drug antibody 24 months
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (MGD013 plus margetuximab) 24 months
Efficacy: Preliminary anti-tumor activity of MGD013 and MGD013 plus margetuximab 36 months
Overall survival Up to 2 years after end of treatment visit
Enrollment 353
Condition
Intervention

Intervention Type: Biological

Intervention Name: MGD013

Description: Anti-PD-1, anti-LAG-3 bispecific DART protein

Other Name: tebotelimab

Intervention Type: Biological

Intervention Name: MGD013 in combination with margetuximab

Description: Anti-PD-1, anti-LAG-3 bispecific DART protein plus anti-HER2 monoclonal antibody

Arm Group Label: MGD013 plus margetuximab

Other Name: tebotelimab in combination with MGAH22

Eligibility

Criteria:

Inclusion Criteria: - Histologically proven, locally advanced unresectable or metastatic solid tumors (or hematologic malignancies, Cohort Expansion only) for whom no approved therapy with demonstrated clinical benefit is available or standard treatment was declined. - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Life expectancy ≥ 12 weeks - Measurable disease - Tissue specimen available for retrospective analysis of PD-1, PD-L1, LAG-3, and MHC-II expression - Acceptable laboratory parameters HER2+ Cohort: - Locally advanced or metastatic HER2+ locally advanced or metastatic solid tumors, regardless of organ of origin. i. The cancer must have progressed following standard therapy, or has progressed during or after HER2-directed therapy if approved and available for patients with HER2+ breast, gastric, or gastroesophageal junction cancer. ii. History of HER2 positivity defined as 3+ by IHC or 2+ by IHC in combination with in situ hybridization (ISH) positivity most recent tumor biopsy. - All patients in the HER2+ cohort must be willing to provide consent for a baseline and on-treatment tumor biopsy during the screening period and within 14 days prior to Cycle 3 Day 1. Exceptions may be made based on a medical contraindication at the discretion of the Sponsor's Medical Monitor. This requirement will be discontinued after an adequate number of samples are collected, as determined by the Sponsor. Exclusion Criteria: - Symptomatic central nervous system (CNS) metastases or primary CNS lymphoma - History of allogeneic bone marrow, stem-cell, or solid organ transplant - History of known or suspected autoimmune disease with the specific exceptions of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic treatment (within the past 2 years), and patients with a history of Grave's disease that are now euthyroid clinically and by laboratory testing. - Treatment with any systemic chemotherapy within 3 weeks prior to the initiation of study drug; treatment with biologics or investigational therapy within the 4 weeks prior to the initiation of study drug. - Major surgery within 4 weeks prior to the initiation of study drug. - Prior treatment with combination of monoclonal antibodies against PD-1 and LAG-3 (Cohort Expansion only). - Treatment with radiation therapy within 2 weeks prior to the initiation of study drug. - Clinically significant cardiovascular disease. - QTcF prolongation > 480 milliseconds - HER2+ cohort: left ventricular ejection fraction less than 50% - Clinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation. - Active pneumonitis or history of non-infectious pneumonitis. - Clinically significant gastrointestinal disorders. - Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug. - Known history of positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome. - Known history of hepatitis B (except in hepatocellular carcinoma) or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction (PCR) - Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed - Dementia or altered mental status that would preclude understanding and rendering of informed consent - 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.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Bradley Sumrow, MD Principal Investigator MacroGenics
Overall Contact

Last Name: Nadia Salem

Phone: 202-834-0910

Email: [email protected]

Location
Facility:
Banner MD Anderson Cancer Center | Gilbert, Arizona, 85234, United States
USC/Norris Comprehensive Cancer Center | Los Angeles, California, 90033, United States
UCLA Hematology & Oncology Clinic | Los Angeles, California, 90095, United States
Hoag Memorial Hospital Presbyterian | Newport Beach, California, 92658, United States
Florida Cancer Specialists & Research Institute | Sarasota, Florida, 34232, United States
University of Chicago Medicine | Chicago, Illinois, 60637, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland, 21287, United States
Massachusetts General Hospital and Dana-Farber Cancer Institute | Boston, Massachusetts, 02215, United States
Duke University Medical Center | Durham, North Carolina, 27710, United States
Stephenson Cancer Center, The University of Oklahoma | Oklahoma City, Oklahoma, 73104, United States
University of Pennsylvania, Abramson Cancer Center | Philadelphia, Pennsylvania, 19104, United States
UPMC Hillman Cancer Center | Pittsburgh, Pennsylvania, 15232, United States
Sarah Cannon Research Institute | Nashville, Tennessee, 37203, United States
The University of Texas M.D. Anderson Cancer Center | Houston, Texas, 77030, United States
St Vincent's Hospital Sydney | Darlinghurst, New South Wales, 2010, Australia
Calvary Mater Newcastle | Waratah, New South Wales, 2298, Australia
Southern Medical Day Care Centre | Wollongong, New South Wales, 2500, Australia
Austin Health Melbourne | Heidelberg, Victoria, 3084, Australia
"Complex Oncology Center - Burgas" EOOD | Burgas, 8000, Bulgaria
"Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda" EAD, Sofia | Sofia, 1407, Bulgaria
Multiprofile Hospital for Active Treatment "Serdika" EOOD, Sofia | Sofia, 1632, Bulgaria
Pratia MCM Kraków | Kraków, Malopolskie, 31-510, Poland
BioVirtus Research Site Sp. Z o.o. / Biovirtus Centrum Medyczne | Józefów, Masovian, 05-410, Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy | Warszawa, Mazowieckie, 02-034, Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy | Warszawa, Mazowieckie, 02-781, Poland
Med-Polonia Sp. z o.o. | Poznań, 60-693, Poland
Vall d'Hebron Institute of Oncology | Barcelona, 08035, Spain
Hospital Ruber Internacional | Madrid, 28034, Spain
START Madrid-CIOCC, Hospital HM Sanchinarro | Madrid, 28050, Spain
King Chulalongkorn Memorial Hospital | Bangkok, 10330, Thailand
Maharaj Nakorn Chiang Mai Hospital | Chiang Mai, 50200, Thailand
Songklanagarind Hospital | Songkhla, 90110, Thailand
Communal Nonprofit Enterprise "Cherkassy Regional Oncology Dispensary" of Cherkassy Regional Council | Cherkassy, Cherkasy Region, 18009, Ukraine
Communal Nonprofit Enterprise Podillia Regional Center of Oncology of Vinnytsia Regional Council | Vinnytsia, Vinnytsa Region, 21029, Ukraine
Communal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council | Dnipro, 49102, Ukraine
Communal Nonprofit Enterprise "Prykarpatsky Clinical Oncological Centre of Ivano-Frankivska Regional Council" | Ivano-Frankivs'k, 76000, Ukraine
Municipal Non-Profit Enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Dispensary" | Sumy, 40022, Ukraine
Communal Nonprofit Enterprise "Central City Clinical Hospital of Uzhhorod City Council", City Oncology Center, State Higher Educational Institution <<Uzhhorod National University>> | Uzhgorod, 88000, Ukraine
Location Countries

Australia

Bulgaria

Poland

Spain

Thailand

Ukraine

United States

Verification Date

2021-08-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: MGD013

Type: Experimental

Description: MGD013 administered IV once every 2 weeks for up to 96 weeks

Label: MGD013 plus margetuximab

Type: Experimental

Description: MGD013 administered in combination with margetuximab IV once every 3 weeks for up to 32 3-week cycles

Patient Data Undecided
Study Design Info

Allocation: Non-Randomized

Intervention Model: Single Group Assignment

Intervention Model Description: Dose escalation followed by Cohort Expansion Phase at the MTD.

Primary Purpose: Treatment

Masking: None (Open Label)

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