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

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.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer; Hematologic Neoplasms; Ovarian Cancer; Non Small Cell Lung Cancer; Advanced Solid Tumors; Squamous Cell Carcinoma of Head and Neck; Cholangiocarcinoma; Small-cell Lung Cancer; TNBC - Triple-Negative Breast Cancer; HER2-positive Advanced Solid Tumors
• Intervention / Treatment: Biological: tebotelimab 1 mg; Biological: tebotelimab 3 mg; Biological: tebotelimab 10 mg; Biological: tebotelimab 30 mg; Biological: tebotelimab 120 mg; Biological: tebotelimab 400 mg; Biological: tebotelimab 600 mg; Biological: tebotelimab 800 mg; Biological: tebotelimab 1200 mg; Biological: tebotelimab 300 mg; Biological: margetuximab

• Study Type: Interventional
• Enrollment (Actual): 277
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
    • Wollongong, New South Wales, Australia, 2500
      • Southern Medical Day Care Centre
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health Melbourne
• Bulgaria
  • Burgas, Bulgaria, 8000
    • "Complex Oncology Center - Burgas" EOOD
  • Sofia, Bulgaria, 1407
    • "Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda" EAD, Sofia
  • Sofia, Bulgaria, 1632
    • Multiprofile Hospital for Active Treatment "Serdika" EOOD, Sofia
• Hong Kong
  • Shatin, Hong Kong
    • Prince of Wales Hospital
• Poland
  • Poznań, Poland, 60-693
    • MED-POLONIA Sp. z o.o.
  • Malopolskie
    • Kraków, Malopolskie, Poland, 31-510
      • Pratia McM Krakow
  • Masovian
    • Józefów, Masovian, Poland, 05-410
      • BioVirtus Research Site Sp. Z o.o. / Biovirtus Centrum Medyczne
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-034
      • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy
    • Warszawa, Mazowieckie, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy
• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institute of Oncology
  • Madrid, Spain, 28034
    • Hospital Ruber Internacional
  • Madrid, Spain, 28050
    • START Madrid-CIOCC, Hospital HM Sanchinarro
• Thailand
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital
• Ukraine
  • Dnipro, Ukraine, 49102
    • Communal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council
  • Ivano-Frankivs'k, Ukraine, 76000
    • Communal Nonprofit Enterprise "Prykarpatsky Clinical Oncological Centre of Ivano-Frankivska Regional Council"
  • Sumy, Ukraine, 40022
    • Municipal Non-Profit Enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Dispensary"
  • Uzhgorod, Ukraine, 88000
    • Communal Nonprofit Enterprise "Central City Clinical Hospital of Uzhhorod City Council", City Oncology Center, State Higher Educational Institution <<Uzhhorod National University>>
  • Cherkasy Region
    • Cherkassy, Cherkasy Region, Ukraine, 18009
      • Communal Nonprofit Enterprise "Cherkassy Regional Oncology Dispensary" of Cherkassy Regional Council
  • Vinnytsa Region
    • Vinnytsia, Vinnytsa Region, Ukraine, 21029
      • Communal Nonprofit Enterprise Podillia Regional Center of Oncology of Vinnytsia Regional Council
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Hematology & Oncology Clinic
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
    • Newport Beach, California, United States, 92658
      • Hoag Memorial Hospital Presbyterian
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists & Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Massachusetts General Hospital and Dana-Farber Cancer Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center, The University of Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania, Abramson Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tebotelimab: 1 mg	Biological: tebotelimab 1 mg; 1 mg IV every other week; Other Names: MGD013
Experimental: Tebotelimab 3 mg	Biological: tebotelimab 3 mg; 3 mg IV every other week; Other Names: MGD013
Experimental: Tebotelimab: 10 mg	Biological: tebotelimab 10 mg; 10 mg IV every other week; Other Names: MGD013
Experimental: Tebotelimab: 30 mg	Biological: tebotelimab 30 mg; 30 mg IV every other week; Other Names: MGD013
Experimental: Tebotelimab: 120 mg	Biological: tebotelimab 120 mg; 120 mg IV every other week; Other Names: MGD013
Experimental: Tebotelimab: 400 mg	Biological: tebotelimab 400 mg; 400 mg IV every other wee; Other Names: MGD013
Experimental: Tebotelimab: 600 mg	Biological: tebotelimab 600 mg; 600 mg IV every other week; Other Names: MGD013
Experimental: Tebotelimab: 800 mg	Biological: tebotelimab 800 mg; 800 mg IV every other week; Other Names: MGD013
Experimental: Tebotelimab: 1200 mg	Biological: tebotelimab 1200 mg; 1200 mg IV every other week; Other Names: MGD013
Experimental: Combination cohort 1; Tebotelimab and margetuximab	Biological: tebotelimab 300 mg; 300 mg IV every other wee; Other Names: MGD013; Biological: margetuximab; 15 mg/kg IV every 3 weeks; Other Names: MGAH22; Margenza
Experimental: Combination Cohort 2; Tebotelimab and margetuximab	Biological: tebotelimab 600 mg; 600 mg IV every other week; Other Names: MGD013; Biological: margetuximab; 15 mg/kg IV every 3 weeks; Other Names: MGAH22; Margenza
Experimental: Monotherapy Cohort Expansion; Monotherapy expansion at 600 mg	Biological: tebotelimab 600 mg; 600 mg IV every other week; Other Names: MGD013

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration versus Time Curve (AUC) of tebotelimab	AUC	From Day 1 to Day 15 after the first and second doses
Maximum Plasma Concentration (Cmax) of tebotelimab and tebotelimab plus margetuximab	Cmax	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	Tmax	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	Ctrough	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	CL	Cycle 1 Day 1 out to Cycle 1 Day 15
Apparent volume of distribution at steady state (Vss) of tebotelimab	Vss	Cycle 1 Day 1 out to Cycle 1 Day 15
Terminal half-life (t1/2) of tebotelimab	t1/2	Cycle 1 Day 1 out to Cycle 1 Day 15
Number of patients with anti-drug antibody	immunogenicity	Study Day 1, 15, 29, 57, 85, 113, then every 56 days up to 2 years Tebotelimab plus margetuximab: Day 1, 22, 43, and then every 6 weeks until treatment discontinuation
Objective response rate (ORR)	ORR is the percentage of participants who have a complete response or a partial response to treatment.	Throughout the study, up to 4 years.
Median 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. Median DoR is the time when 50% of responders are still in response.	Throughout the study, up to 4 years.
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. Median PFS is the time when 50% of participants remain free of PD or death.	Throughout the study, up to 4 years.
Median Overall survival (OS)	OS is defined as the time from the first dose date to the date of death from any cause. Median OS is the time when 50% of participants are still alive.	Throughout the study, up to 4 years.

Collaborators and Investigators

• Sponsor: MacroGenics
• Investigators: Study Director: Ashley Ward, MD, MacroGenics

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2017
• Primary Completion (Actual): February 8, 2023
• Study Completion (Actual): February 8, 2023

Study Registration Dates

• First Submitted: July 12, 2017
• First Submitted That Met QC Criteria: July 14, 2017
• First Posted (Actual): July 17, 2017

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Hematologic Diseases; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Head and Neck Neoplasms; Neoplastic Processes; Carcinoma, Squamous Cell; Breast Neoplasms; Neoplasms; Hematologic Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Small Cell Lung Carcinoma; Squamous Cell Carcinoma of Head and Neck; Cholangiocarcinoma; Triple Negative Breast Neoplasms; Antineoplastic Agents; Margetuximab
• Other Study ID Numbers: CP-MGD013-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No