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Advanced Solid TumorsPhase 1NCT03219268

A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms

A Phase 1 study testing tebotelimab 1 mg, tebotelimab 3 mg and tebotelimab 10 mg in people with Advanced Solid Tumors and Hematologic Neoplasms, run by MacroGenics at 40 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
tebotelimab 1 mg, tebotelimab 3 mg and tebotelimab 10 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
277 participants
Where
40 sitesin 8 countries
Study dates
18 Aug 2017to 8 Feb 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • HER2+ Cohort:
  • Locally advanced or metastatic HER2+ locally advanced or metastatic solid tumors, regardless of organ of origin.
  • 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.
  • 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.

Who cannot join

  • 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).
Show all 19Show fewer
  • 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.

Trial locations and contacts

40 sites in 8 countries.

40 sites in 8 countries

United States15 sites

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21287

  • Massachusetts General Hospital and Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Chicago Medicine

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • The University of Texas M.D. Anderson Cancer Center

    Houston, Texas, 77030

  • USC/Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • UCLA Hematology & Oncology Clinic

    Los Angeles, California, 90095

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Hoag Memorial Hospital Presbyterian

    Newport Beach, California, 92658

  • Stephenson Cancer Center, The University of Oklahoma

    Oklahoma City, Oklahoma, 73104

  • University of Pennsylvania, Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Florida Cancer Specialists & Research Institute

    Sarasota, Florida, 34232

Other trials in United States

Ukraine6 sites

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

    Cherkassy, Cherkasy Oblast, 18009

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

    Dnipro, 49102

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

    Ivano-Frankivsk, 76000

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

    Sumy, 40022

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

    Uzhhorod, 88000

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

    Vinnytsia, Vinnytsa Region, 21029

Other trials in Ukraine

Poland5 sites

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

    Józefów, Masovian Voivodeship, 05-410

  • Pratia MCM Kraków

    Krakow, Lesser Poland Voivodeship, 31-510

  • Med-Polonia Sp. z o.o.

    Poznan, 60-693

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

    Warsaw, Masovian Voivodeship, 02-034

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

    Warsaw, Masovian Voivodeship, 02-781

Other trials in Poland

Australia4 sites

  • St Vincent's Hospital Sydney

    Darlinghurst, New South Wales, 2010

  • Austin Health Melbourne

    Heidelberg, Victoria, 3084

  • Calvary Mater Newcastle

    Waratah, New South Wales, 2298

  • Southern Medical Day Care Centre

    Wollongong, New South Wales, 2500

Other trials in Australia

Bulgaria3 sites

  • "Complex Oncology Center - Burgas" EOOD

    Burgas, 8000

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

    Sofia, 1407

  • Multiprofile Hospital for Active Treatment "Serdika" EOOD, Sofia

    Sofia, 1632

Other trials in Bulgaria

Spain3 sites

  • Vall d'Hebron Institute of Oncology

    Barcelona, 08035

  • Hospital Ruber Internacional

    Madrid, 28034

  • START Madrid-CIOCC, Hospital HM Sanchinarro

    Madrid, 28050

Other trials in Spain

Thailand3 sites

  • King Chulalongkorn Memorial Hospital

    Bangkok, 10330

  • Maharaj Nakorn Chiang Mai Hospital

    Chiang Mai, 50200

  • Songklanagarind Hospital

    Songkhla, 90110

Other trials in Thailand

Hong Kong1 site

  • Prince of Wales Hospital

    Shatin

Other trials in Hong Kong

About this study

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

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.

Being tested
tebotelimab 1 mg, tebotelimab 3 mg, tebotelimab 10 mg, tebotelimab 30 mg, tebotelimab 120 mg
Medical subject headings
Hematologic Neoplasms, Ovarian Neoplasms, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma, Squamous Cell Carcinoma of Head and Neck, Cholangiocarcinoma, Uterine Cervical Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tebotelimab 1 mgBiological

    Also called MGD013

    1 mg IV every other week

  • tebotelimab 3 mgBiological

    Also called MGD013

    3 mg IV every other week

  • tebotelimab 10 mgBiological

    Also called MGD013

    10 mg IV every other week

  • tebotelimab 30 mgBiological

    Also called MGD013

    30 mg IV every other week

  • tebotelimab 120 mgBiological

    Also called MGD013

    120 mg IV every other week

  • tebotelimab 300 mgBiological

    Also called MGD013

    300 mg IV every other wee

  • tebotelimab 400 mgBiological

    Also called MGD013

    400 mg IV every other wee

  • tebotelimab 600 mgBiological

    Also called MGD013

    600 mg IV every other week

  • tebotelimab 800 mgBiological

    Also called MGD013

    800 mg IV every other week

  • tebotelimab 1200 mgBiological

    Also called MGD013

    1200 mg IV every other week

  • margetuximabBiological

    Also called MGAH22, Margenza

    15 mg/kg IV every 3 weeks

Study groups in NCT03219268
Study groupRoleWhat they receive
Tebotelimab: 1 mgExperimentalNot described
Receives: Biological: tebotelimab 1 mg
Tebotelimab 3 mgExperimentalNot described
Receives: Biological: tebotelimab 3 mg
Tebotelimab: 10 mgExperimentalNot described
Receives: Biological: tebotelimab 10 mg
Tebotelimab: 30 mgExperimentalNot described
Receives: Biological: tebotelimab 30 mg
Tebotelimab: 120 mgExperimentalNot described
Receives: Biological: tebotelimab 120 mg
Tebotelimab: 400 mgExperimentalNot described
Receives: Biological: tebotelimab 400 mg
Tebotelimab: 600 mgExperimentalNot described
Receives: Biological: tebotelimab 600 mg
Tebotelimab: 800 mgExperimentalNot described
Receives: Biological: tebotelimab 800 mg
Tebotelimab: 1200 mgExperimentalNot described
Receives: Biological: tebotelimab 1200 mg
Combination cohort 1ExperimentalTebotelimab and margetuximab
Receives: Biological: tebotelimab 300 mg; Biological: margetuximab
Combination Cohort 2ExperimentalTebotelimab and margetuximab
Receives: Biological: tebotelimab 600 mg; Biological: margetuximab
Monotherapy Cohort ExpansionExperimentalMonotherapy expansion at 600 mg
Receives: Biological: tebotelimab 600 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: up to 24 months

  2. Number of participants with Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (tebotelimab plus margetuximab)

    Safety

    Measured: up to 24 months

Secondary outcomes (12)

  1. Area Under the Plasma Concentration versus Time Curve (AUC) of tebotelimab

    AUC

    Measured: From Day 1 to Day 15 after the first and second doses

  2. Maximum Plasma Concentration (Cmax) of tebotelimab and tebotelimab plus margetuximab

    Cmax

    Measured: 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

  3. Time to reach maximum (peak) plasma concentration (Tmax) of tebotelimab and tebotelimab plus margetuximab

    Tmax

    Measured: 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

  4. Trough plasma concentration (Ctrough) of tebotelimab

    Ctrough

    Measured: 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

  5. Total body clearance of the drug from plasma (CL) of tebotelimab

    CL

    Measured: Cycle 1 Day 1 out to Cycle 1 Day 15

  6. Apparent volume of distribution at steady state (Vss) of tebotelimab

    Vss

    Measured: Cycle 1 Day 1 out to Cycle 1 Day 15

  7. Terminal half-life (t1/2) of tebotelimab

    t1/2

    Measured: Cycle 1 Day 1 out to Cycle 1 Day 15

  8. Number of patients with anti-drug antibody

    immunogenicity

    Measured: 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

  9. Objective response rate (ORR)

    ORR is the percentage of participants who have a complete response or a partial response to treatment.

    Measured: Throughout the study, up to 4 years.

  10. 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.

    Measured: Throughout the study, up to 4 years.

  11. 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.

    Measured: Throughout the study, up to 4 years.

  12. 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.

    Measured: Throughout the study, up to 4 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2017
  2. Study start18 Aug 2017
  3. Primary completion8 Feb 2023
  4. Study completion8 Feb 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
277 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03219268
Sponsor's protocol ID
CP-MGD013-01
Status last verified
Dec 2023
First submitted
12 Jul 2017
Last updated
21 Dec 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37857711

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing tebotelimab 1 mg, tebotelimab 3 mg and tebotelimab 10 mg in people with Advanced Solid Tumors and Hematologic Neoplasms, run by MacroGenics at 40 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States, Ukraine, Poland, Australia, Bulgaria and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with Treatment-Emergent Adverse Events (TEAE) as assessed by CTCAE v4.03 (tebotelimab monotherapy) (time frame: up to 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03219268, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2023.

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