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
1 other identifier
interventional
277
8 countries
40
Brief Summary
The primary goal of this Phase 1 study is to characterize the safety and tolerability of tebotelimab and establish the maximum tolerated dose (MTD) of tebotelimab in advanced solid tumors, and tebotelimab in combination with margetuximab in HER2+ advanced solid tumors. Pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and the anti-tumor activity of tebotelimab will also be assessed.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2017
Longer than P75 for phase_1
40 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 12, 2017
CompletedFirst Posted
Study publicly available on registry
July 17, 2017
CompletedStudy Start
First participant enrolled
August 18, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 8, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
February 8, 2023
CompletedDecember 21, 2023
December 1, 2023
5.5 years
July 12, 2017
December 19, 2023
Conditions
Outcome Measures
Primary Outcomes (2)
Number of participants with Treatment-Emergent Adverse Events (TEAE) as assessed by CTCAE v4.03 (tebotelimab monotherapy)
Safety 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.
up to 24 months
Number of participants with Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (tebotelimab plus margetuximab)
Safety
up to 24 months
Secondary Outcomes (12)
Area Under the Plasma Concentration versus Time Curve (AUC) of tebotelimab
From Day 1 to Day 15 after the first and second doses
Maximum Plasma Concentration (Cmax) of tebotelimab and tebotelimab plus margetuximab
At the end of infusion on Study Days 1, 15, 29 and 43 in Cycles 1 and 2 and on Study Day 1 for all subsequent cycles until treatment discontinuation, up to 2 years
Time to reach maximum (peak) plasma concentration (Tmax) of tebotelimab and tebotelimab plus margetuximab
At the end of infusion on Study Days 1, 15, 29 and 43 in Cycles 1 and 2 and on Study Day 1 for all subsequent cycles until treatment discontinuation, up to 2 years
Trough plasma concentration (Ctrough) of tebotelimab
Study Days 1, 15, 29, 43 in Cycles 1 and 2 and Day 1 of each subsequent cycle s until treatment discontinuation, up to 2 years
Total body clearance of the drug from plasma (CL) of tebotelimab
Cycle 1 Day 1 out to Cycle 1 Day 15
- +7 more secondary outcomes
Study Arms (12)
Tebotelimab: 1 mg
EXPERIMENTALTebotelimab 3 mg
EXPERIMENTALTebotelimab: 10 mg
EXPERIMENTALTebotelimab: 30 mg
EXPERIMENTALTebotelimab: 120 mg
EXPERIMENTALTebotelimab: 400 mg
EXPERIMENTALTebotelimab: 600 mg
EXPERIMENTALTebotelimab: 800 mg
EXPERIMENTALTebotelimab: 1200 mg
EXPERIMENTALCombination cohort 1
EXPERIMENTALTebotelimab and margetuximab
Combination Cohort 2
EXPERIMENTALTebotelimab and margetuximab
Monotherapy Cohort Expansion
EXPERIMENTALMonotherapy expansion at 600 mg
Interventions
600 mg IV every other week
15 mg/kg IV every 3 weeks
Eligibility Criteria
You may qualify if:
- 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 Immunohistochemistry (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.
You may not qualify if:
- 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.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MacroGenicslead
Study Sites (40)
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
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, 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
Prince of Wales Hospital
Shatin, Hong Kong
Pratia MCM Kraków
Krakow, Lesser Poland Voivodeship, 31-510, Poland
BioVirtus Research Site Sp. Z o.o. / Biovirtus Centrum Medyczne
Józefów, Masovian Voivodeship, 05-410, Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy
Warsaw, Masovian Voivodeship, 02-034, Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy
Warsaw, Masovian Voivodeship, 02-781, Poland
Med-Polonia Sp. z o.o.
Poznan, 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 Oblast, 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-Frankivsk, 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>>
Uzhhorod, 88000, Ukraine
Related Publications (1)
Luke JJ, Patel MR, Blumenschein GR, Hamilton E, Chmielowski B, Ulahannan SV, Connolly RM, Santa-Maria CA, Wang J, Bahadur SW, Weickhardt A, Asch AS, Mallesara G, Clingan P, Dlugosz-Danecka M, Tomaszewska-Kiecana M, Pylypenko H, Hamad N, Kindler HL, Sumrow BJ, Kaminker P, Chen FZ, Zhang X, Shah K, Smith DH, De Costa A, Li J, Li H, Sun J, Moore PA. The PD-1- and LAG-3-targeting bispecific molecule tebotelimab in solid tumors and hematologic cancers: a phase 1 trial. Nat Med. 2023 Nov;29(11):2814-2824. doi: 10.1038/s41591-023-02593-0. Epub 2023 Oct 19.
PMID: 37857711DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Ashley Ward, MD
MacroGenics
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
July 12, 2017
First Posted
July 17, 2017
Study Start
August 18, 2017
Primary Completion
February 8, 2023
Study Completion
February 8, 2023
Last Updated
December 21, 2023
Record last verified: 2023-12
Data Sharing
- IPD Sharing
- Will not share