A Study of MGD013 in Patients With Unresectable or Metastatic Neoplasms
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| ClinicalTrials.gov Identifier: NCT03219268 |
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Recruitment Status :
Completed
First Posted : July 17, 2017
Last Update Posted : December 21, 2023
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Sponsor:
MacroGenics
Information provided by (Responsible Party):
MacroGenics
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Biological: tebotelimab 1 mg Biological: tebotelimab 3 mg Biological: tebotelimab 10 mg Biological: tebotelimab 30 mg Biological: tebotelimab 120 mg Biological: tebotelimab 300 mg Biological: tebotelimab 400 mg Biological: tebotelimab 600 mg Biological: tebotelimab 800 mg Biological: tebotelimab 1200 mg Biological: margetuximab | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 277 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | August 18, 2017 |
| Actual Primary Completion Date : | February 8, 2023 |
| Actual Study Completion Date : | February 8, 2023 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
| Experimental: Tebotelimab: 1 mg |
Biological: tebotelimab 1 mg
1 mg IV every other week
Other Name: MGD013 |
| Experimental: Tebotelimab 3 mg |
Biological: tebotelimab 3 mg
3 mg IV every other week
Other Name: MGD013 |
| Experimental: Tebotelimab: 10 mg |
Biological: tebotelimab 10 mg
10 mg IV every other week
Other Name: MGD013 |
| Experimental: Tebotelimab: 30 mg |
Biological: tebotelimab 30 mg
30 mg IV every other week
Other Name: MGD013 |
| Experimental: Tebotelimab: 120 mg |
Biological: tebotelimab 120 mg
120 mg IV every other week
Other Name: MGD013 |
| Experimental: Tebotelimab: 400 mg |
Biological: tebotelimab 400 mg
400 mg IV every other wee
Other Name: MGD013 |
| Experimental: Tebotelimab: 600 mg |
Biological: tebotelimab 600 mg
600 mg IV every other week
Other Name: MGD013 |
| Experimental: Tebotelimab: 800 mg |
Biological: tebotelimab 800 mg
800 mg IV every other week
Other Name: MGD013 |
| Experimental: Tebotelimab: 1200 mg |
Biological: tebotelimab 1200 mg
1200 mg IV every other week
Other Name: MGD013 |
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Experimental: Combination cohort 1
Tebotelimab and margetuximab
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Biological: tebotelimab 300 mg
300 mg IV every other wee
Other Name: MGD013 Biological: margetuximab 15 mg/kg IV every 3 weeks
Other Names:
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Experimental: Combination Cohort 2
Tebotelimab and margetuximab
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Biological: tebotelimab 600 mg
600 mg IV every other week
Other Name: MGD013 Biological: margetuximab 15 mg/kg IV every 3 weeks
Other Names:
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Experimental: Monotherapy Cohort Expansion
Monotherapy expansion at 600 mg
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Biological: tebotelimab 600 mg
600 mg IV every other week
Other Name: MGD013 |
Primary Outcome Measures :
- Number of participants with Treatment-Emergent Adverse Events (TEAE) as assessed by CTCAE v4.03 (tebotelimab monotherapy) [ Time Frame: 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) [ Time Frame: up to 24 months ]Safety
Secondary Outcome Measures :
- Area Under the Plasma Concentration versus Time Curve (AUC) of tebotelimab [ Time Frame: From Day 1 to Day 15 after the first and second doses ]AUC
- Maximum Plasma Concentration (Cmax) of tebotelimab and tebotelimab plus margetuximab [ Time Frame: 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
- Time to reach maximum (peak) plasma concentration (Tmax) of tebotelimab and tebotelimab plus margetuximab [ Time Frame: 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
- Trough plasma concentration (Ctrough) of tebotelimab [ Time Frame: 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
- Total body clearance of the drug from plasma (CL) of tebotelimab [ Time Frame: Cycle 1 Day 1 out to Cycle 1 Day 15 ]CL
- Apparent volume of distribution at steady state (Vss) of tebotelimab [ Time Frame: Cycle 1 Day 1 out to Cycle 1 Day 15 ]Vss
- Terminal half-life (t1/2) of tebotelimab [ Time Frame: Cycle 1 Day 1 out to Cycle 1 Day 15 ]t1/2
- Number of patients with anti-drug antibody [ Time Frame: 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
- Objective response rate (ORR) [ Time Frame: Throughout the study, up to 4 years. ]ORR is the percentage of participants who have a complete response or a partial response to treatment.
- Median Duration of response (DoR) [ Time Frame: 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.
- Progression-free survival (PFS) [ Time Frame: 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) [ Time Frame: 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.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03219268
Locations
Show 40 study locations
Sponsors and Collaborators
MacroGenics
Investigators
| Study Director: | Ashley Ward, MD | MacroGenics |
| Responsible Party: | MacroGenics |
| ClinicalTrials.gov Identifier: | NCT03219268 |
| Other Study ID Numbers: |
CP-MGD013-01 |
| First Posted: | July 17, 2017 Key Record Dates |
| Last Update Posted: | December 21, 2023 |
| Last Verified: | December 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Neoplasms Lung Neoplasms Small Cell Lung Carcinoma Triple Negative Breast Neoplasms Cholangiocarcinoma Squamous Cell Carcinoma of Head and Neck Hematologic Neoplasms Neoplasm Metastasis Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms |
Carcinoma, Squamous Cell Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Breast Neoplasms Breast Diseases Skin Diseases Adenocarcinoma Head and Neck Neoplasms Hematologic Diseases Neoplastic Processes Pathologic Processes Margetuximab Antineoplastic Agents |