Sponsor: MacroGenics (industry)
Phase: 1
Start date: March 6, 2024
Planned enrollment: 230
Last updated in HealthScout: Dec 2024
MGC026, also known as SYNtecan E, is an investigational antibody-drug conjugate (ADC) developed by MacroGenics. It targets B7-H3, a protein overexpressed in various solid tumors. (macrogenics.com)
MGC026 comprises a B7-H3-targeting antibody linked to a novel topoisomerase I inhibitor-based payload, exatecan, using Synaffix's GlycoConnect™ technology. This design aims to deliver the cytotoxic agent directly to cancer cells expressing B7-H3, potentially reducing off-target effects. (aacrjournals.org)
A Phase 1 dose-escalation study (NCT06242470) is currently recruiting participants with advanced solid tumors to evaluate the safety, pharmacokinetics, and preliminary efficacy of MGC026. (clinconnect.io)
In preclinical studies, MGC026 demonstrated potent antitumor activity in B7-H3-positive tumor xenografts, including lung, pancreatic, and prostate cancers, as well as head and neck squamous cell carcinoma and melanoma. The ADC was well tolerated in cynomolgus monkeys at exposure levels exceeding those required for antitumor activity, with no observed lung toxicity. (aacrjournals.org)
Last updated: Apr 2025
MGC026, also known as SYNtecan E, is an investigational antibody-drug conjugate (ADC) developed by MacroGenics. It targets B7-H3, a protein overexpressed in various solid tumors. (macrogenics.com)
MGC026 comprises a B7-H3-targeting antibody linked to a novel topoisomerase I inhibitor-based payload, exatecan, using Synaffix's GlycoConnect™ technology. This design aims to deliver the cytotoxic agent directly to cancer cells expressing B7-H3, potentially reducing off-target effects. (aacrjournals.org)
A Phase 1 dose-escalation study (NCT06242470) is currently recruiting participants with advanced solid tumors to evaluate the safety, pharmacokinetics, and preliminary efficacy of MGC026. (clinconnect.io)
In preclinical studies, MGC026 demonstrated potent antitumor activity in B7-H3-positive tumor xenografts, including lung, pancreatic, and prostate cancers, as well as head and neck squamous cell carcinoma and melanoma. The ADC was well tolerated in cynomolgus monkeys at exposure levels exceeding those required for antitumor activity, with no observed lung toxicity. (aacrjournals.org)
Last updated: Apr 2025
As of April 30, 2025, there is limited publicly available information regarding the clinical trial NCT06242470, titled "A Phase 1/1b First-in-Human, Open Label, Dose Escalation and Cohort Expansion Study of MGC026 in Participants With Advanced Solid Tumors." The trial is currently ongoing, and detailed results or analyses have not been published.
For the most current information, it is recommended to consult official clinical trial registries or contact the study sponsors directly.
Last updated: Apr 2025
Goal: The primary objective of this Phase 1/1b trial is to evaluate the safety and tolerability of the investigational drug MGC026 in patients with advanced solid tumors. The study also aims to assess the pharmacokinetics, immunogenicity, and preliminary antitumor activity of the drug.
Patients: The trial involves adult participants aged 18 years or older who have unresectable, locally advanced or metastatic solid tumors. Eligible cancers include various types, such as squamous cell cancer of the head and neck, small cell lung cancer, squamous and non-squamous non-small cell lung cancer, colorectal cancer, hepatocellular cancer, and others. Participants must meet certain performance and laboratory parameters and must not be pregnant or breastfeeding.
Design: The structure of the study is non-randomized, consisting of both dose escalation and cohort expansion phases. It is an open-label study, meaning both researchers and participants are aware of the treatment being administered.
Treatments: The study administers MGC026, an investigational drug given by IV infusion, which is intended as a treatment for relapsed or refractory advanced solid tumors. This trial aims to identify a range of safe and effective dosing regimens for the drug, which targets specific tumor types to potentially inhibit cancer growth. Initial preclinical studies suggest MGC026 shows promising antitumor activities, although detailed results in humans are still pending. Participants can receive up to 35 treatments, contingent upon the absence of severe adverse effects or disease progression.
Outcomes: The study's primary outcome is the incidence of adverse and serious adverse events among participants. Secondary outcomes include overall and disease-specific response rates, duration of response in various tumor types, pharmacokinetic measures such as maximum serum concentration and area under the time concentration curve, and the development of anti-MGC026 antibodies.
Burden on patient: This trial is expected to impose a significant burden on patients due to the frequent monitoring requirements typical of a Phase 1 study. Participants will undergo routine laboratory testing, pharmacokinetics blood draws, and monitoring for side effects and cancer progression. The intravenous administration of MGC026 at varying doses necessitates regular hospital visits, exacting vigilance for adverse effects, and compliance with protocol-specified intervals for assessments and treatments, which can be demanding for the patient.
Inclusion Criteria:
* Adults ≥ 18 years old, able to provide informed consent
* Adequate performance and laboratory parameters
* Unresectable, locally advanced or metastatic solid tumors including: squamous cell cancer (SCC) of the head and neck, esophageal SCC, squamous and non-squamous non-small cell lung cancer, small cell lung cancer, bladder cancer, sarcoma, endometrial cancer, melanoma, castration resistant prostate cancer, breast cancer, ovarian cancer, cervical cancer, colorectal cancer gastric or gastroesophageal cancer, pancreatic carcinoma, clear cell renal cell cancer or hepatocellular cancer.
* Measurable disease per RECIST v1.1. Participants with metastatic CRPC without measurable disease are eligible.
* Must be willing to use highly effective methods of birth control from the time of consent through 7 months after discontinuation of MGC026.
* Not pregnant or breastfeeding.
Exclusion Criteria:
* Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures.
* Another cancer that required treatment within the past 2 years, with the exception of those with low risk of cancer spreading or death such as adequately treated non melanomatous skin cancer, localized prostate cancer (Gleason Score \< 6), or carcinoma in situ.
* Patients with history of prior central nervous system (CNS) metastasis must have been treated, be asymptomatic, and not have concurrent treatment for CNS disease, progression of CNS metastases on magnetic resonance imaging, computed tomography or positron emission tomography, or history of leptomeningeal disease or cord compression at the time of enrollment.
* Treatment with surgery, systemic cancer therapy, immunotherapy, chimeric antigen receptor-T therapy, or anti-hormonal within protocol specified intervals.
* Prior autologous or allogeneic stem cell or solid organ transplant.
* Clinically significant cardiovascular, pulmonary, or gastrointestinal disorders.
* Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 1 week of first study drug administration.
* Known history of hepatitis B or C infection or known positive test for hepatitis B surface antigen or core antigen, or hepatitis C polymerase chain reaction.
* Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
* History of primary immunodeficiency.
* Major trauma or major surgery within 4 weeks of first study drug administration.
* Known hypersensitivity to recombinant proteins.
Auchenflower, Queensland, 4066, Australia
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Status: Recruiting
Kurralta Park, South Australia, 5037, Australia
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Status: Recruiting
Heidelberg, Victoria, 3084, Australia
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Status: Recruiting
Sutton, SM2 5PT, United Kingdom
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Status: Recruiting
Oxford, OX3 9DU, United Kingdom
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Status: Recruiting
Los Angeles, California, 90025, United States
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Status: Recruiting
Grand Rapids, Michigan, 49546, United States
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Status: Recruiting
Portland, Oregon, 97213, United States
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Status: Recruiting
Houston, Texas, 77030, United States
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Status: Recruiting
Houston, Texas, 77030, United States
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Status: Recruiting
West Valley City, Utah, 84119, United States
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Status: Recruiting