A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms

Phase 1

Completed

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

• Registration Number: NCT03219268
• Lead Sponsor: MacroGenics

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-07-12
• Study First Submitted QC: 2017-07-14
• Study First Posted: 2017-07-17
• Study Start: 2017-08-18
• Primary Completion: 2023-02-08
• Study Completion: 2023-02-08
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-19
• Last Update Posted: 2023-12-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 277

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Combination Cohort 2	margetuximab	Tebotelimab and margetuximab
Combination Cohort 2	tebotelimab 600 mg	Tebotelimab and margetuximab
Tebotelimab: 30 mg	tebotelimab 30 mg	-
Tebotelimab 3 mg	tebotelimab 3 mg	-
Tebotelimab: 400 mg	tebotelimab 400 mg	-
Tebotelimab: 1 mg	tebotelimab 1 mg	-
Tebotelimab: 600 mg	tebotelimab 600 mg	-
Tebotelimab: 10 mg	tebotelimab 10 mg	-
Tebotelimab: 120 mg	tebotelimab 120 mg	-
Tebotelimab: 800 mg	tebotelimab 800 mg	-
Combination cohort 1	margetuximab	Tebotelimab and margetuximab
Tebotelimab: 1200 mg	tebotelimab 1200 mg	-
Combination cohort 1	tebotelimab 300 mg	Tebotelimab and margetuximab
Monotherapy Cohort Expansion	tebotelimab 600 mg	Monotherapy expansion at 600 mg

Primary Outcome Measures

Name	Time	Method
Number of participants with Treatment-Emergent Adverse Events (TEAE) as assessed by CTCAE v4.03 (tebotelimab monotherapy)	up to 24 months	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.
Number of participants with Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (tebotelimab plus margetuximab)	up to 24 months	Safety

Secondary Outcome Measures

Name	Time	Method
Number of patients with anti-drug antibody	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	immunogenicity
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	Cmax
Total body clearance of the drug from plasma (CL) of tebotelimab	Cycle 1 Day 1 out to Cycle 1 Day 15	CL
Terminal half-life (t1/2) of tebotelimab	Cycle 1 Day 1 out to Cycle 1 Day 15	t1/2
Median Duration of response (DoR)	Throughout the study, up to 4 years.	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.
Area Under the Plasma Concentration versus Time Curve (AUC) of tebotelimab	From Day 1 to Day 15 after the first and second doses	AUC
Apparent volume of distribution at steady state (Vss) of tebotelimab	Cycle 1 Day 1 out to Cycle 1 Day 15	Vss
Objective response rate (ORR)	Throughout the study, up to 4 years.	ORR is the percentage of participants who have a complete response or a partial response to treatment.
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	Ctrough
Progression-free survival (PFS)	Throughout the study, up to 4 years.	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.
Median Overall survival (OS)	Throughout the study, up to 4 years.	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.
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	Tmax

Trial Locations

Locations (39)

University of Chicago Medicine; 🇺🇸 Chicago, Illinois, United States

"Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda" EAD, Sofia; 🇧🇬 Sofia, Bulgaria

Med-Polonia Sp. z o.o.; 🇵🇱 Poznań, Poland

Communal Nonprofit Enterprise "Prykarpatsky Clinical Oncological Centre of Ivano-Frankivska Regional Council"; 🇺🇦 Ivano-Frankivs'k, Ukraine

Southern Medical Day Care Centre; 🇦🇺 Wollongong, New South Wales, Australia

Multiprofile Hospital for Active Treatment "Serdika" EOOD, Sofia; 🇧🇬 Sofia, Bulgaria

Songklanagarind Hospital; 🇹🇭 Songkhla, Thailand

Calvary Mater Newcastle; 🇦🇺 Waratah, New South Wales, Australia

King Chulalongkorn Memorial Hospital; 🇹🇭 Bangkok, Thailand

Maharaj Nakorn Chiang Mai Hospital; 🇹🇭 Chiang Mai, Thailand

Hospital Ruber Internacional; 🇪🇸 Madrid, Spain

USC/Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

UCLA Hematology & Oncology Clinic; 🇺🇸 Los Angeles, California, United States

University of Pennsylvania, Abramson Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

Hoag Memorial Hospital Presbyterian; 🇺🇸 Newport Beach, California, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States

Florida Cancer Specialists & Research Institute; 🇺🇸 Sarasota, Florida, United States

Massachusetts General Hospital and Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

The University of Texas M.D. Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

St Vincent's Hospital Sydney; 🇦🇺 Darlinghurst, New South Wales, Australia

Austin Health Melbourne; 🇦🇺 Heidelberg, Victoria, Australia

"Complex Oncology Center - Burgas" EOOD; 🇧🇬 Burgas, Bulgaria

Pratia MCM Kraków; 🇵🇱 Kraków, Malopolskie, Poland

BioVirtus Research Site Sp. Z o.o. / Biovirtus Centrum Medyczne; 🇵🇱 Józefów, Masovian, Poland

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy; 🇵🇱 Warszawa, Mazowieckie, Poland

Vall d'Hebron Institute of Oncology; 🇪🇸 Barcelona, Spain

START Madrid-CIOCC, Hospital HM Sanchinarro; 🇪🇸 Madrid, Spain

Communal Nonprofit Enterprise "Cherkassy Regional Oncology Dispensary" of Cherkassy Regional Council; 🇺🇦 Cherkassy, Cherkasy Region, Ukraine

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Stephenson Cancer Center, The University of Oklahoma; 🇺🇸 Oklahoma City, Oklahoma, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

Communal Nonprofit Enterprise Podillia Regional Center of Oncology of Vinnytsia Regional Council; 🇺🇦 Vinnytsia, Vinnytsa Region, Ukraine

Communal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council; 🇺🇦 Dnipro, Ukraine

Municipal Non-Profit Enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Dispensary"; 🇺🇦 Sumy, Ukraine

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

Prince of Wales Hospital; 🇭🇰 Shatin, Hong Kong