MGC026 for Cancer

Recruiting at 10 trial locations

Overseen By Global Trial Manager

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: MacroGenics

Disqualifiers: CNS metastasis, Cardiovascular disorders, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called MGC026 for individuals with solid tumors that cannot be removed or have spread despite previous treatments. Researchers aim to assess the treatment's safety, its effects on the body, and its potential to shrink tumors. Participants with advanced cancers, such as lung, bladder, or breast cancer, that have recurred or are not improving with other treatments may be suitable candidates. The treatment is administered through an IV, and researchers will monitor patient responses and any side effects. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that treatment with certain therapies within specific intervals before the trial may affect eligibility, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that MGC026 is likely to be safe for humans?

Research shows that MGC026, a treatment being tested for certain types of cancer, has undergone studies for safety and patient tolerance. MGC026 is an ADC (antibody-drug conjugate) that targets the B7-H3 protein, found in many tumors.

In earlier studies, safety information for MGC026 aligned with previous results. These studies found that patients generally tolerated the treatment well, with no unexpected or severe side effects causing major concerns. However, like any drug, some side effects can occur, and patients are closely monitored for any negative reactions.

MGC026 remains in the early stages of testing, so not all safety aspects are known yet. Its progression to this phase of testing suggests that initial safety results were promising enough to continue research. Participants in these studies receive regular check-ups to ensure any side effects are quickly managed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about MGC026 for cancer treatment because it introduces a novel approach by targeting B7-H3, a protein not commonly addressed by current therapies. This treatment is a topoisomerase 1 inhibitor (TOP1i)-based antibody-drug conjugate (ADC), which combines a targeted antibody with a potent anti-cancer drug, allowing it to directly attack cancer cells with precision. Unlike traditional chemotherapy, which affects both healthy and cancerous cells, MGC026 aims to minimize damage to normal tissues, potentially reducing side effects. By specifically focusing on B7-H3, MGC026 offers a promising new avenue for treating cancers that overexpress this protein, paving the way for more personalized and effective cancer treatments.

What evidence suggests that MGC026 might be an effective treatment for cancer?

Research shows that MGC026 is designed to find and destroy cancer cells by linking a special antibody to a potent drug. This combination, known as an antibody-drug conjugate (ADC), specifically targets B7-H3, a protein present on many cancer cells. Studies have shown that ADCs like MGC026 can effectively kill cancer cells in early tests, particularly in prostate cancer. The drug contains a substance that prevents cancer cells from dividing and growing. Initial results suggest that MGC026 has promising effects against tumors, although it remains in the early stages of testing. Participants in this trial will receive MGC026 in one of the various experimental cohorts to further evaluate its effectiveness and safety. ^{1 4 6 7 8}

Who Is on the Research Team?

Denise Casey, MD

Principal Investigator

MacroGenics

Are You a Good Fit for This Trial?

Adults over 18 with advanced solid tumors that can't be removed by surgery, including various cancers like lung, prostate, bladder, and more. They must measure their disease progress using RECIST v1.1 criteria and agree to use effective birth control methods. Pregnant or breastfeeding individuals cannot participate.

Inclusion Criteria

Not pregnant or breastfeeding

Adequate performance and laboratory parameters

Must be willing to use highly effective methods of birth control from the time of consent through 7 months after discontinuation of MGC026

Exclusion Criteria

History of primary immunodeficiency

Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome

I have a history of hepatitis B or C, or tested positive for it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive MGC026 by intravenous infusion with dose escalation to determine safety and tolerability

21-day cycles, up to 1 year

Day 1 of every 21-day cycle

Cohort Expansion

Participants receive MGC026 to further evaluate safety and preliminary antitumor activity

21-day cycles, up to 1 year

Day 1 of every 21-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 135 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MGC026

Trial Overview The trial is testing MGC026's safety and effectiveness against different advanced solid tumors. Participants will receive up to 35 IV infusions of MGC026 in increasing doses until side effects become severe or the cancer worsens.

How Is the Trial Designed?

Group I: Expansion cohort 4 Experimental Treatment 1 Intervention

Group II: Expansion cohort 3 Experimental Treatment 1 Intervention

Group III: Expansion cohort 2 Experimental Treatment 1 Intervention

Group IV: Expansion cohort 1 Experimental Treatment 1 Intervention

Group V: Expansion Cohort 6 Experimental Treatment 1 Intervention

Group VI: Expansion Cohort 5 Experimental Treatment 1 Intervention

Group VII: Cohort 6 Experimental Treatment 1 Intervention

Group VIII: Cohort 5 Experimental Treatment 1 Intervention

Group IX: Cohort 4 Experimental Treatment 1 Intervention

Group X: Cohort 3 Experimental Treatment 1 Intervention

Group XI: Cohort 2 Experimental Treatment 1 Intervention

Group XII: Cohort 1 Experimental Treatment 1 Intervention

MGC026 is a topoisomerase 1 inhibitor (TOP1i)-based ADC that targets B7-H3 administered IV every 3 weeks.

Who Is Running the Clinical Trial?

MacroGenics

Lead Sponsor

Trials

51

Recruited

5,400+

Published Research Related to This Trial

In a safety lead-in phase involving 30 patients with BRAF V600E-mutant metastatic colorectal cancer, the combination therapy of encorafenib, binimetinib, and cetuximab showed manageable safety, with dose-limiting toxicities occurring in 5 patients, including serious but reversible side effects.

The treatment demonstrated promising efficacy, with a 48% overall response rate, median progression-free survival of 8.0 months, and median overall survival of 15.3 months, suggesting it could become a new standard of care for this patient population if confirmed in further trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients With BRAF V600E-Mutant Metastatic Colorectal Cancer: Safety Lead-In Results From the Phase III BEACON Colorectal Cancer Study. Van Cutsem, E., Huijberts, S., Grothey, A., et al.[2021]

Regorafenib, a multikinase inhibitor used for advanced solid tumors, was associated with a range of adverse events (AEs) in a meta-analysis of 2,065 patients, with the most common being hand-foot skin reaction (54%), diarrhea (33%), and fatigue (32%).

The analysis revealed that regorafenib significantly increases the risk of developing AEs compared to placebo, highlighting the importance of monitoring these effects to improve patient safety and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events risk associated with regorafenib in the treatment of advanced solid tumors: meta-analysis of randomized controlled trials. Yin, X., Yin, Y., Shen, C., et al.[2022]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

A total of 3120 adverse event cases related to avapritinib were reported to the FDA, with 44% occurring within the first 30 days of treatment, highlighting the importance of monitoring patients closely during this period.

The study found that elderly male patients are at a higher risk for serious adverse events, indicating that clinicians should exercise caution when prescribing avapritinib to this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. Rong, L., Xie, M., Jiang, M., et al.[2023]

In a study of 116 patients with metastatic melanoma treated with PD-1 inhibitors, the overall survival rate at 12 months was 70.2%, with a median overall survival of 27.9 months, indicating effective treatment outcomes in a real-world setting.

The study found that while 55.2% of patients experienced immune-related adverse events (AEs), these AEs were associated with improved overall survival, suggesting that the presence of these side effects may indicate a positive response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data on PD-1 inhibitor therapy in metastatic melanoma. Arheden, A., Skalenius, J., Bjursten, S., et al.[2019]

Citations

1. macrogenics.com macrogenics.com/pipeline/mgc026/

MGC026 (B7-H3 ADC) MGC026 is an investigational, clinical ADC incorporating a B7-H3-targeting antibody and a novel topoisomerase I inhibitor-based linker-payload, SYNtecan E™.

2. aacrjournals.org aacrjournals.org/mct/article/24/10_Supplement/A140/766562/Abstract-A140-MGC026-a-glycan-linked-exatecan

Abstract A140: MGC026, a glycan-linked, exatecan-based ... MGC026, a glycan-linked, exatecan-based antibody-drug conjugate (ADC) targeting B7-H3, is efficacious toward prostate cancer patient-derived ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06242470

NCT06242470 | A Study of MGC026 in Participants With ... The study is designed to understand the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of MGC026 in participants ...

4. macrogenics.com macrogenics.com/wp-content/uploads/2024/12/AACR-2024-Poster-Preclinical-Development-of-MGC026-B7-H3-ADC.pdf

MGC026 Results Abstract B7-H3 Conclusions Results Page 1. Preclinical Development of MGC026, a Glycan-linked,. Exatecan-based Antibody-drug Conjugate (ADC) Targeting B7-H3 for Solid Cancer.

5. nature.com nature.com/articles/s41591-025-03600-2

A B7H3-targeting antibody–drug conjugate in advanced ... ADCs targeting B7H3, such as MGC018, DS7300a, HS-20093 and MHB088C, have shown promising results in clinical trials, yet there are no approved ...

6. ir.macrogenics.com ir.macrogenics.com/news-releases/news-release-details/macrogenics-provides-update-corporate-progress-and-2024

MacroGenics Provides Update on Corporate Progress and ... MGC026 is a TOP1i-based ADC that targets B7-H3, an antigen with broad ... Safety data from the study remained consistent with prior data disclosures.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3035

Results from a phase 1/2 study of 7MW3711: A novel B7- ... Here we present the safety and efficacy data of 7MW3711 ... (ADC) incorporating a topoisomerase I inhibitor in patients with lung cancer.

8. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/2362/738805/Abstract-2362-Preclinical-efficacy-and-safety-of

Abstract 2362: Preclinical efficacy and safety of M9140, a ... M9140 is the first clinical-stage TOP1 inhibitor payload ADC directed against CEACAM5, which is expressed in colorectal cancer (CRC) and other cancer ...