MGC028 for Solid Tumors

Recruiting at 5 trial locations

Overseen By Global Trial Manager

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: MacroGenics

Disqualifiers: Active brain metastases, Prior transplant, Active infection, others

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

Compensation: Varies

Number of Visits: 6

Duration: 18 weeks

124 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to characterize the safety, tolerability, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) or maximum administered dose of MGC028 (if no MTD is defined). The study will enroll adult participants with relapsed or refractory, unresectable, locally advanced of metastatic solid tumors known to express ADAM9. The main question the study aims to answer is: * What types of side effects will participants experience when receiving MGC028? * Can MGC028 cause cancer to shrink, remain stable, or able to control disease progression of participants with advanced solid tumors? Participants will * Undergo screening procedures to determine eligibility * Receive study treatments initially every 3 weeks. * Have blood samples taken for routine and research tests * Have other examinations to check heart and lung function, and general health status * Be asked about any side effects that may be happening or other medications you are taking. The study doctor will provide treatment for side effects, if necessary. * Have the study doctor assess your tumor status at regular intervals to determine how you are responding to treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you should discuss all your medications with the study doctor, as they will assess any potential interactions or necessary adjustments.

What safety data exists for MGC028 (also known as MGI-114 or irofulven) in humans?

MGI-114 (also known as irofulven) has been tested in humans for safety, showing some side effects like blood-related issues (granulocytopenia and thrombocytopenia) and mental health effects (hallucination, depression/anxiety, and insomnia). ^{1 2 3 4 5}

What makes the drug MGC028 unique for treating solid tumors?

MGC028 is unique because it targets myeloid-derived suppressor cells (MDSCs), which are immune cells that help tumors grow by suppressing the body's immune response. By focusing on these cells, MGC028 aims to enhance the effectiveness of cancer immunotherapy, which is different from traditional treatments that do not specifically target the immune-suppressing environment around tumors. ^{6 7 8 9 10}

Research Team

Pepi Pencheva, M.D.

Principal Investigator

MacroGenics

Eligibility Criteria

Adults with advanced solid tumors that can't be removed by surgery, like certain types of lung, bile duct, and pancreatic cancers. They must have tried standard treatments without success or couldn't tolerate them. Participants need at least one measurable tumor and should not have had more than two prior chemotherapy treatments for their advanced disease.

Inclusion Criteria

I have NSCLC or pancreatic cancer with limited prior treatments.

My health and lab results meet the study's requirements.

Participants of childbearing potential must agree to use highly effective methods of birth control

Exclusion Criteria

I haven't had treatment for another cancer, except for certain low-risk types, in the past 2 years.

I have active brain or leptomeningeal metastases.

I do not have any ongoing infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive study treatments every 3 weeks, with assessments of tumor status and monitoring for side effects

18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 25 months

Expansion Cohort

Participants receive the maximum tolerated dose or maximum administered dose of MGC028

Variable

Treatment Details

Interventions

• MGC028

Trial Overview The trial is testing MGC028 to see if it's safe and what the highest dose patients can take without serious side effects is. It also looks at whether MGC028 can shrink tumors or control cancer progression in those with specific advanced solid tumors expressing ADAM9.

Participant Groups

Group I: Expansion Cohort 3 Experimental Treatment 1 Intervention

MTD or MAD of MGC028, IV

Group II: Expansion Cohort 2 Experimental Treatment 1 Intervention

MTD or MAD of MGC028, IV

Group III: Expansion Cohort 1 Experimental Treatment 1 Intervention

MTD or MAD of MGC028, IV

Group IV: Cohort 6 Experimental Treatment 1 Intervention

Dose level 6 of MGC028, IV

Group V: Cohort 5 Experimental Treatment 1 Intervention

Dose level 5 of MGC028, IV

Group VI: Cohort 4 Experimental Treatment 1 Intervention

Dose level 4 of MGC028, IV

Group VII: Cohort 3 Experimental Treatment 1 Intervention

Dose level 3 of MGC028, IV

Group VIII: Cohort 2 Experimental Treatment 1 Intervention

Dose level 2 of MGC028, IV

Group IX: Cohort 1 Experimental Treatment 1 Intervention

Dose level 1 of MGC028, IV

Who Is Running the Clinical Trial?

MacroGenics

Lead Sponsor

Trials

51

Recruited

5,400+

Findings from Research

In a study involving 15 patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone chemotherapy, the novel antitumor agent MGI-114 showed no objective tumor responses, leading to the conclusion that it is not effective as a second-line treatment.

The treatment was associated with significant side effects, including grade 2 or higher thrombocytopenia in 40% of patients, and grade 3 nausea and grade 2 vomiting in 40% and 47% of patients, respectively, indicating safety concerns with this dosing regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with advanced non-small cell cancer previously treated with chemotherapy. Dowell, JE., Johnson, DH., Rogers, JS., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Methylglyoxal-bis(guanylhydrazone) (Methyl-GAG): current status and future prospects. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with advanced non-small cell cancer previously treated with chemotherapy. [2019]

3. France pubmed.ncbi.nlm.nih.gov

Treatment response, survival, and safety profile of camrelizumab plus apatinib regimen as third-line treatment in metastatic gastric cancer patients. [2022]

4. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of Cytotoxic Agents After Progression on Anti-PD-(L)1 Antibody for Pre-treated Metastatic Gastric Cancer. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Phase II study of MGI-114 administered intravenously for 5 days every 28 days to patients with metastatic colorectal cancer. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

MDSCs in cancer: Conceiving new prognostic and therapeutic targets. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Targeting immune suppressing myeloid-derived suppressor cells in oncology. [2021]

8. Australia pubmed.ncbi.nlm.nih.gov

Increased circulating GrMyeloid-derived suppressor cells correlated with tumor burden and survival in locally advanced cervical cancer patient. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Modulations in the Peripheral Immune System of Glioblastoma Patient Is Connected to Therapy and Tumor Progression-A Case Report from the IMMO-GLIO-01 Trial. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Increased myeloid-derived suppressor cells in gastric cancer correlate with cancer stage and plasma S100A8/A9 proinflammatory proteins. [2022]