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 :
Recruiting
First Posted : July 17, 2017
Last Update Posted : July 15, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Solid Tumors Hematologic Neoplasms Gastric Cancer Ovarian Cancer GastroEsophageal Cancer HER2-positive Breast Cancer HER2-positive Gastric Cancer DLBCL | Biological: MGD013 Biological: MGD013 in combination with margetuximab | Phase 1 |
This is a Phase 1, open-label, dose escalation and cohort expansion study designed to characterize the safety, tolerability, PK, PD, immunogenicity, and preliminary antitumor activity of MGD013 administered by IV infusion every 2 weeks. The study consists of a Dose Escalation Phase to determine the MTD or maximum administered dose (MAD) of MGD013 if no MTD is defined, followed by a Cohort Expansion Phase to further define the safety and initial antitumor activity of MGD013 with the dose established in the Dose Escalation Phase.
In the Dose Escalation Phase, MGD013 will be evaluated in sequential escalating flat doses in successive cohorts of 1 to 6 patients each. Upon completion of the Dose Escalation Phase, a Cohort Expansion Phase will be initiated at the MTD/MAD.
Patients with unresectable, locally advanced or metastatic solid tumors of any histology will be enrolled in the Dose Escalation Phase. The Cohort Expansion Phase will be limited to selected cohorts of patients with unresectable, locally advanced or metastatic solid tumors or hematologic malignancies for whom there is no available therapy likely to confer clinical benefit. Two additional cohorts will enroll patients with gastric/gastroesophageal cancer or epithelial ovarian cancer, with MGD013 given every 3 weeks.
A separate cohort will evaluate the combination of MGD013 with margetuximab (anti-HER2 monoclonal antibody) in approximately 99 patients, in subgroups with HER2-positive gastric or gastroesophageal cancer, HER2-positive breast cancer, and any other HER2-positive cancer.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 445 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Intervention Model Description: | Dose escalation followed by Cohort Expansion Phase at the MTD. |
| 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 |
| Estimated Primary Completion Date : | July 2021 |
| Estimated Study Completion Date : | August 2022 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: MGD013
MGD013 administered IV once every 2 or 3 weeks for up to 96 weeks
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Biological: MGD013
Anti-PD-1, anti-LAG-3 bispecific DART protein |
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Experimental: MGD013 plus margetuximab
MGD013 administered in combination with margetuximab IV once every 3 weeks for up to 32 3-week cycles
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Biological: MGD013
Anti-PD-1, anti-LAG-3 bispecific DART protein Biological: MGD013 in combination with margetuximab Anti-PD-1, anti-LAG-3 bispecific DART protein plus anti-HER2 monoclonal antibody
Other Name: MGAH22 |
- Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (MGD013 monotherapy) [ Time Frame: 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.
- Maximum Tolerated Dose [ Time Frame: 24 months ]maximum tolerated or maximum administered dose of MGD013
- Area Under the Plasma Concentration versus Time Curve (AUC) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]AUC
- Maximum Plasma Concentration (Cmax) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]Cmax
- Time to reach maximum (peak) plasma concentration (Tmax) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]Tmax
- Trough plasma concentration (Ctrough) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]Ctrough
- Total body clearance of the drug from plasma (CL) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]CL
- Apparent volume of distribution at steady state (Vss) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]Vss
- Terminal half-life (t1/2) of MGD013 and MGD013 plus margetuximab [ Time Frame: 24 months ]t1/2
- Percent of patients with anti-drug antibody [ Time Frame: 24 months ]immunogenicity
- Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (MGD013 plus margetuximab) [ Time Frame: 24 months ]Safety
- Efficacy: Preliminary anti-tumor activity of MGD013 and MGD013 plus margetuximab [ Time Frame: 36 months ]Preliminary anti-tumor activity of MGD013 and MGD013 plus margetuximab
- Overall survival [ Time Frame: Up to 2 years after end of treatment visit ]Time from start of treatment to death
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 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
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
| Contact: Nadia Salem | 202-834-0910 | salemn@Macrogenics.com | |
| Contact: Janine Koucheki | (240) 224-4457 | kouchekij@macrogenics.com |
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| Principal Investigator: | Bradley Sumrow, 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: | July 15, 2020 |
| Last Verified: | July 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Neoplasms Stomach Neoplasms Hematologic Neoplasms Neoplasm Metastasis Neoplasms by Site Gastrointestinal Neoplasms Digestive System Neoplasms |
Digestive System Diseases Gastrointestinal Diseases Stomach Diseases Hematologic Diseases Neoplastic Processes Pathologic Processes |