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

230 Participants Needed

Trial Summary

What is the purpose of this trial?

The study is designed to understand the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of MGC026 in participants with relapsed or refractory, unresectable, locally advanced or metastatic solid tumors The study has a dose escalation portion and a cohort expansion portion of the study. Participants will receive MGC026 by intravenous (IV) infusion. The dose of MGC026 will be assigned at the time of enrollment. Participants may receive up to 35 treatments if there are no severe side effects and as long as the cancer does not get worse. Participants will be monitored for side effects, and progression of cancer, have blood samples collected for routing laboratory work, and blood samples collected for research purposes.

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.

What safety data exists for molecular target anticancer drugs like MGC026?

Molecular target anticancer drugs, which may include treatments like MGC026, have been shown to significantly increase the risk of serious adverse events (SAEs) and fatal adverse events (FAEs) compared to placebo. In a large analysis, the overall incidence of SAEs was about 27%, and FAEs was about 2.3%, indicating a need for careful monitoring to prevent these events. ^{1 2 3 4 5}

Research Team

Denise Casey, MD

Principal Investigator

MacroGenics

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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: Cohort 6 Experimental Treatment 1 Intervention

Group VI: Cohort 5 Experimental Treatment 1 Intervention

Group VII: Cohort 4 Experimental Treatment 1 Intervention

Group VIII: Cohort 3 Experimental Treatment 1 Intervention

Group IX: Cohort 2 Experimental Treatment 1 Intervention

Group X: Cohort 1 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

MacroGenics

Lead Sponsor

Trials

51

Recruited

5,400+

Findings from Research

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 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]

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]

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]

References

1. India 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. [2020]

2. England 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. [2023]

3. United States 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Real-world data on PD-1 inhibitor therapy in metastatic melanoma. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Adverse events risk associated with regorafenib in the treatment of advanced solid tumors: meta-analysis of randomized controlled trials. [2022]