A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03219268
• Other study ID #: CP-MGD013-01
• Status: Completed
• Phase: Phase 1
• Start date: August 18, 2017
• Est. completion date: February 8, 2023

Study information

• Verified date: December 2023
• Source: MacroGenics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 277
• Est. completion date: February 8, 2023
• Est. primary completion date: February 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Biological:
• tebotelimab 1 mg
1 mg IV every other week
• tebotelimab 3 mg
3 mg IV every other week
• tebotelimab 10 mg
10 mg IV every other week
• tebotelimab 30 mg
30 mg IV every other week
• tebotelimab 120 mg
120 mg IV every other week
• tebotelimab 300 mg
300 mg IV every other wee
• tebotelimab 400 mg
400 mg IV every other wee
• tebotelimab 600 mg
600 mg IV every other week
• tebotelimab 800 mg
800 mg IV every other week
• tebotelimab 1200 mg
1200 mg IV every other week
• margetuximab
15 mg/kg IV every 3 weeks

Locations

Country	Name	City	State
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Austin Health Melbourne	Heidelberg	Victoria
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Southern Medical Day Care Centre	Wollongong	New South Wales
Bulgaria	"Complex Oncology Center - Burgas" EOOD	Burgas
Bulgaria	"Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda" EAD, Sofia	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment "Serdika" EOOD, Sofia	Sofia
Hong Kong	Prince of Wales Hospital	Shatin
Poland	BioVirtus Research Site Sp. Z o.o. / Biovirtus Centrum Medyczne	Józefów	Masovian
Poland	Pratia MCM Kraków	Kraków	Malopolskie
Poland	Med-Polonia Sp. z o.o.	Poznan
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy	Warszawa	Mazowieckie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy	Warszawa	Mazowieckie
Spain	Vall d'Hebron Institute of Oncology	Barcelona
Spain	Hospital Ruber Internacional	Madrid
Spain	START Madrid-CIOCC, Hospital HM Sanchinarro	Madrid
Thailand	King Chulalongkorn Memorial Hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital	Chiang Mai
Thailand	Songklanagarind Hospital	Songkhla
Ukraine	Communal Nonprofit Enterprise "Cherkassy Regional Oncology Dispensary" of Cherkassy Regional Council	Cherkassy	Cherkasy Region
Ukraine	Communal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council	Dnipro
Ukraine	Communal Nonprofit Enterprise "Prykarpatsky Clinical Oncological Centre of Ivano-Frankivska Regional Council"	Ivano-Frankivs'k
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	Communal Nonprofit Enterprise Podillia Regional Center of Oncology of Vinnytsia Regional Council	Vinnytsia	Vinnytsa Region
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Massachusetts General Hospital and Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago Medicine	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	The University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	UCLA Hematology & Oncology Clinic	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Stephenson Cancer Center, The University of Oklahoma	Oklahoma City	Oklahoma
United States	University of Pennsylvania, Abramson Cancer Center	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Florida Cancer Specialists & Research Institute	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Hong Kong,  Poland,  Spain,  Thailand,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of participants with Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (tebotelimab plus margetuximab)	Safety	up to 24 months
Secondary	Area Under the Plasma Concentration versus Time Curve (AUC) of tebotelimab	AUC	From Day 1 to Day 15 after the first and second doses
Secondary	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
Secondary	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
Secondary	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
Secondary	Total body clearance of the drug from plasma (CL) of tebotelimab	CL	Cycle 1 Day 1 out to Cycle 1 Day 15
Secondary	Apparent volume of distribution at steady state (Vss) of tebotelimab	Vss	Cycle 1 Day 1 out to Cycle 1 Day 15
Secondary	Terminal half-life (t1/2) of tebotelimab	t1/2	Cycle 1 Day 1 out to Cycle 1 Day 15
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.