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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03219268




Registration number
NCT03219268
Ethics application status
Date submitted
12/07/2017
Date registered
17/07/2017

Titles & IDs
Public title
A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms
Scientific 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
Secondary ID [1] 0 0
CP-MGD013-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Hematologic Neoplasms 0 0
Ovarian Cancer 0 0
HER2-positive Advanced Solid Tumors 0 0
Non Small Cell Lung Cancer 0 0
Small-cell Lung Cancer 0 0
Squamous Cell Carcinoma of Head and Neck 0 0
Cholangiocarcinoma 0 0
Cervical Cancer 0 0
TNBC - Triple-Negative Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Head and neck
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - tebotelimab 1 mg
Treatment: Other - tebotelimab 3 mg
Treatment: Other - tebotelimab 10 mg
Treatment: Other - tebotelimab 30 mg
Treatment: Other - tebotelimab 120 mg
Treatment: Other - tebotelimab 300 mg
Treatment: Other - tebotelimab 400 mg
Treatment: Other - tebotelimab 600 mg
Treatment: Other - tebotelimab 800 mg
Treatment: Other - tebotelimab 1200 mg
Treatment: Other - margetuximab

Experimental: Tebotelimab: 1 mg -

Experimental: Tebotelimab 3 mg -

Experimental: Tebotelimab: 10 mg -

Experimental: Tebotelimab: 30 mg -

Experimental: Tebotelimab: 120 mg -

Experimental: Tebotelimab: 400 mg -

Experimental: Tebotelimab: 600 mg -

Experimental: Tebotelimab: 800 mg -

Experimental: Tebotelimab: 1200 mg -

Experimental: Combination cohort 1 - Tebotelimab and margetuximab

Experimental: Combination Cohort 2 - Tebotelimab and margetuximab

Experimental: Monotherapy Cohort Expansion - Monotherapy expansion at 600 mg


Treatment: Other: tebotelimab 1 mg
1 mg IV every other week

Treatment: Other: tebotelimab 3 mg
3 mg IV every other week

Treatment: Other: tebotelimab 10 mg
10 mg IV every other week

Treatment: Other: tebotelimab 30 mg
30 mg IV every other week

Treatment: Other: tebotelimab 120 mg
120 mg IV every other week

Treatment: Other: tebotelimab 300 mg
300 mg IV every other wee

Treatment: Other: tebotelimab 400 mg
400 mg IV every other wee

Treatment: Other: tebotelimab 600 mg
600 mg IV every other week

Treatment: Other: tebotelimab 800 mg
800 mg IV every other week

Treatment: Other: tebotelimab 1200 mg
1200 mg IV every other week

Treatment: Other: margetuximab
15 mg/kg IV every 3 weeks
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with Treatment-Emergent Adverse Events (TEAE) as assessed by CTCAE v4.03 (tebotelimab monotherapy)
Timepoint [1] 0 0
up to 24 months
Primary outcome [2] 0 0
Number of participants with Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (tebotelimab plus margetuximab)
Timepoint [2] 0 0
up to 24 months
Secondary outcome [1] 0 0
Area Under the Plasma Concentration versus Time Curve (AUC) of tebotelimab
Timepoint [1] 0 0
From Day 1 to Day 15 after the first and second doses
Secondary outcome [2] 0 0
Maximum Plasma Concentration (Cmax) of tebotelimab and tebotelimab plus margetuximab
Timepoint [2] 0 0
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 outcome [3] 0 0
Time to reach maximum (peak) plasma concentration (Tmax) of tebotelimab and tebotelimab plus margetuximab
Timepoint [3] 0 0
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 outcome [4] 0 0
Trough plasma concentration (Ctrough) of tebotelimab
Timepoint [4] 0 0
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 outcome [5] 0 0
Total body clearance of the drug from plasma (CL) of tebotelimab
Timepoint [5] 0 0
Cycle 1 Day 1 out to Cycle 1 Day 15
Secondary outcome [6] 0 0
Apparent volume of distribution at steady state (Vss) of tebotelimab
Timepoint [6] 0 0
Cycle 1 Day 1 out to Cycle 1 Day 15
Secondary outcome [7] 0 0
Terminal half-life (t1/2) of tebotelimab
Timepoint [7] 0 0
Cycle 1 Day 1 out to Cycle 1 Day 15
Secondary outcome [8] 0 0
Number of patients with anti-drug antibody
Timepoint [8] 0 0
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 outcome [9] 0 0
Objective response rate (ORR)
Timepoint [9] 0 0
Throughout the study, up to 4 years.
Secondary outcome [10] 0 0
Median Duration of response (DoR)
Timepoint [10] 0 0
Throughout the study, up to 4 years.
Secondary outcome [11] 0 0
Progression-free survival (PFS)
Timepoint [11] 0 0
Throughout the study, up to 4 years.
Secondary outcome [12] 0 0
Median Overall survival (OS)
Timepoint [12] 0 0
Throughout the study, up to 4 years.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/08/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/02/2023
Sample size
Target
Accrual to date
Final
277
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 0 0
Southern Medical Day Care Centre - Wollongong
Recruitment hospital [4] 0 0
Austin Health Melbourne - Heidelberg
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Oklahoma
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Bulgaria
State/province [13] 0 0
Burgas
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Sofia
Country [15] 0 0
Hong Kong
State/province [15] 0 0
Shatin
Country [16] 0 0
Poland
State/province [16] 0 0
Malopolskie
Country [17] 0 0
Poland
State/province [17] 0 0
Masovian
Country [18] 0 0
Poland
State/province [18] 0 0
Mazowieckie
Country [19] 0 0
Poland
State/province [19] 0 0
Poznan
Country [20] 0 0
Spain
State/province [20] 0 0
Barcelona
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Thailand
State/province [22] 0 0
Bangkok
Country [23] 0 0
Thailand
State/province [23] 0 0
Chiang Mai
Country [24] 0 0
Thailand
State/province [24] 0 0
Songkhla
Country [25] 0 0
Ukraine
State/province [25] 0 0
Cherkasy Region
Country [26] 0 0
Ukraine
State/province [26] 0 0
Vinnytsa Region
Country [27] 0 0
Ukraine
State/province [27] 0 0
Dnipro
Country [28] 0 0
Ukraine
State/province [28] 0 0
Ivano-Frankivs'k
Country [29] 0 0
Ukraine
State/province [29] 0 0
Sumy
Country [30] 0 0
Ukraine
State/province [30] 0 0
Uzhgorod

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
MacroGenics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ashley Ward, MD
Address 0 0
MacroGenics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03219268