A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms

NCT ID: NCT03219268

Last Updated: 2023-12-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

277 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-08-18

Study Completion Date

2023-02-08

Brief Summary

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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.

Detailed Description

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Conditions

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Advanced Solid Tumors Hematologic Neoplasms Ovarian Cancer HER2-positive Advanced Solid Tumors Non Small Cell Lung Cancer Small-cell Lung Cancer Squamous Cell Carcinoma of Head and Neck Cholangiocarcinoma Cervical Cancer TNBC - Triple-Negative Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Tebotelimab: 1 mg

Group Type EXPERIMENTAL

tebotelimab 1 mg

Intervention Type BIOLOGICAL

1 mg IV every other week

Tebotelimab 3 mg

Group Type EXPERIMENTAL

tebotelimab 3 mg

Intervention Type BIOLOGICAL

3 mg IV every other week

Tebotelimab: 10 mg

Group Type EXPERIMENTAL

tebotelimab 10 mg

Intervention Type BIOLOGICAL

10 mg IV every other week

Tebotelimab: 30 mg

Group Type EXPERIMENTAL

tebotelimab 30 mg

Intervention Type BIOLOGICAL

30 mg IV every other week

Tebotelimab: 120 mg

Group Type EXPERIMENTAL

tebotelimab 120 mg

Intervention Type BIOLOGICAL

120 mg IV every other week

Tebotelimab: 400 mg

Group Type EXPERIMENTAL

tebotelimab 400 mg

Intervention Type BIOLOGICAL

400 mg IV every other wee

Tebotelimab: 600 mg

Group Type EXPERIMENTAL

tebotelimab 600 mg

Intervention Type BIOLOGICAL

600 mg IV every other week

Tebotelimab: 800 mg

Group Type EXPERIMENTAL

tebotelimab 800 mg

Intervention Type BIOLOGICAL

800 mg IV every other week

Tebotelimab: 1200 mg

Group Type EXPERIMENTAL

tebotelimab 1200 mg

Intervention Type BIOLOGICAL

1200 mg IV every other week

Combination cohort 1

Tebotelimab and margetuximab

Group Type EXPERIMENTAL

tebotelimab 300 mg

Intervention Type BIOLOGICAL

300 mg IV every other wee

margetuximab

Intervention Type BIOLOGICAL

15 mg/kg IV every 3 weeks

Combination Cohort 2

Tebotelimab and margetuximab

Group Type EXPERIMENTAL

tebotelimab 600 mg

Intervention Type BIOLOGICAL

600 mg IV every other week

margetuximab

Intervention Type BIOLOGICAL

15 mg/kg IV every 3 weeks

Monotherapy Cohort Expansion

Monotherapy expansion at 600 mg

Group Type EXPERIMENTAL

tebotelimab 600 mg

Intervention Type BIOLOGICAL

600 mg IV every other week

Interventions

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tebotelimab 1 mg

1 mg IV every other week

Intervention Type BIOLOGICAL

tebotelimab 3 mg

3 mg IV every other week

Intervention Type BIOLOGICAL

tebotelimab 10 mg

10 mg IV every other week

Intervention Type BIOLOGICAL

tebotelimab 30 mg

30 mg IV every other week

Intervention Type BIOLOGICAL

tebotelimab 120 mg

120 mg IV every other week

Intervention Type BIOLOGICAL

tebotelimab 300 mg

300 mg IV every other wee

Intervention Type BIOLOGICAL

tebotelimab 400 mg

400 mg IV every other wee

Intervention Type BIOLOGICAL

tebotelimab 600 mg

600 mg IV every other week

Intervention Type BIOLOGICAL

tebotelimab 800 mg

800 mg IV every other week

Intervention Type BIOLOGICAL

tebotelimab 1200 mg

1200 mg IV every other week

Intervention Type BIOLOGICAL

margetuximab

15 mg/kg IV every 3 weeks

Intervention Type BIOLOGICAL

Other Intervention Names

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MGD013 MGD013 MGD013 MGD013 MGD013 MGD013 MGD013 MGD013 MGD013 MGD013 MGAH22 Margenza

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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MacroGenics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ashley Ward, MD

Role: STUDY_DIRECTOR

MacroGenics

Locations

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Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UCLA Hematology & Oncology Clinic

Los Angeles, California, United States

Site Status

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status

Florida Cancer Specialists & Research Institute

Sarasota, Florida, United States

Site Status

University of Chicago Medicine

Chicago, Illinois, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital and Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Stephenson Cancer Center, The University of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Site Status

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Site Status

Southern Medical Day Care Centre

Wollongong, New South Wales, Australia

Site Status

Austin Health Melbourne

Heidelberg, Victoria, Australia

Site Status

"Complex Oncology Center - Burgas" EOOD

Burgas, , Bulgaria

Site Status

"Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda" EAD, Sofia

Sofia, , Bulgaria

Site Status

Multiprofile Hospital for Active Treatment "Serdika" EOOD, Sofia

Sofia, , Bulgaria

Site Status

Prince of Wales Hospital

Shatin, , Hong Kong

Site Status

Pratia MCM Kraków

Krakow, Lesser Poland Voivodeship, Poland

Site Status

BioVirtus Research Site Sp. Z o.o. / Biovirtus Centrum Medyczne

Józefów, Masovian Voivodeship, Poland

Site Status

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy

Warsaw, Masovian Voivodeship, Poland

Site Status

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy

Warsaw, Masovian Voivodeship, Poland

Site Status

Med-Polonia Sp. z o.o.

Poznan, , Poland

Site Status

Vall d'Hebron Institute of Oncology

Barcelona, , Spain

Site Status

Hospital Ruber Internacional

Madrid, , Spain

Site Status

START Madrid-CIOCC, Hospital HM Sanchinarro

Madrid, , Spain

Site Status

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Site Status

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, , Thailand

Site Status

Songklanagarind Hospital

Songkhla, , Thailand

Site Status

Communal Nonprofit Enterprise "Cherkassy Regional Oncology Dispensary" of Cherkassy Regional Council

Cherkassy, Cherkasy Oblast, Ukraine

Site Status

Communal Nonprofit Enterprise Podillia Regional Center of Oncology of Vinnytsia Regional Council

Vinnytsia, Vinnytsa Region, Ukraine

Site Status

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

Dnipro, , Ukraine

Site Status

Communal Nonprofit Enterprise "Prykarpatsky Clinical Oncological Centre of Ivano-Frankivska Regional Council"

Ivano-Frankivsk, , Ukraine

Site Status

Municipal Non-Profit Enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Dispensary"

Sumy, , Ukraine

Site Status

Communal Nonprofit Enterprise "Central City Clinical Hospital of Uzhhorod City Council", City Oncology Center, State Higher Educational Institution <<Uzhhorod National University>>

Uzhhorod, , Ukraine

Site Status

Countries

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United States Australia Bulgaria Hong Kong Poland Spain Thailand Ukraine

References

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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.

Reference Type DERIVED
PMID: 37857711 (View on PubMed)

Other Identifiers

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CP-MGD013-01

Identifier Type: -

Identifier Source: org_study_id