A Study of MGC028 in Participants With Advanced Solid Tumors
A Phase 1, First-in-Human, Open Label, Dose Escalation and Cohort Expansion Study of MGC028 in Participants With Advanced Solid Tumors
1 other identifier
interventional
124
1 country
7
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2025
Typical duration for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 4, 2024
CompletedFirst Posted
Study publicly available on registry
December 9, 2024
CompletedStudy Start
First participant enrolled
February 13, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2027
April 27, 2026
April 1, 2026
1.7 years
December 4, 2024
April 23, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Number and Types of Adverse Events (AEs) in Participants Receiving MGC028
Types of AEs include Serious Adverse Events (SAEs), and AEs Leading to Treatment Delay or Discontinuation or Dose Reduction, dose limiting toxicities, and AEs of Special Interest. Observation of side effects determines the highest safe dose for further study
Throughout the study treatment and safety follow up period, up to 25 months
Secondary Outcomes (8)
Mean maximum concentration of MGC028 antibody
Through Cycle 6 of the study, approximately 18 weeks
Mean Area Under the Concentration Time Curve of MGC028 antibody
Through Cycle 6 of the study, approximately 18 weeks
Number of Participants Who Develop Anti-Drug Antibodies to MGC028
Throughout the study treatment period, up to 2 years
Objective Response Rate (ORR)
Throughout the study and follow up period, up to 2.5 years.
Median Duration of Response
Throughout the study and follow up period, up to 2.5 years.
- +3 more secondary outcomes
Study Arms (9)
Cohort 1
EXPERIMENTALDose level 1 of MGC028, IV
Cohort 2
EXPERIMENTALDose level 2 of MGC028, IV
Cohort 3
EXPERIMENTALDose level 3 of MGC028, IV
Cohort 4
EXPERIMENTALDose level 4 of MGC028, IV
Cohort 5
EXPERIMENTALDose level 5 of MGC028, IV
Cohort 6
EXPERIMENTALDose level 6 of MGC028, IV
Expansion Cohort 1
EXPERIMENTALMTD or MAD of MGC028, IV
Expansion Cohort 2
EXPERIMENTALMTD or MAD of MGC028, IV
Expansion Cohort 3
EXPERIMENTALMTD or MAD of MGC028, IV
Interventions
MGC028 is an antibody-drug conjugate targeted against ADAM9.
Eligibility Criteria
You may qualify if:
- Participants in dose escalation or supplemental cohorts must have histologically proven unresectable, locally advanced or metastatic solid tumor limited to one of the following types: NSCLC adenocarcinoma, cholangiocarcinoma, colorectal carcinoma (CRC), or pancreatic carcinoma that is refractory to standard therapy, or for which standard therapy does not exist, has proven to be intolerable, or has been refused by the participant.
- Participants in expansion cohorts must have either
- NSCLC adenocarcinoma with
- progression on or following anti-PD-1/PD-L1 inhibitor, unless contraindicated
- progression on or following therapy for actionable mutations (e.g. EGFR or ALK mutations), if present
- no more than 2 prior lines of cytotoxic chemotherapy for advanced or metastatic disease.
- Pancreatic cancer
- following at least 1 systemic therapy
- no more than 2 prior lines of cytotoxic therapy for advanced or metastatic disease.
- Colorectal adenocarcinoma with
- Progression during or following standard therapy with a fluoropyrimidine-based chemotherapy, oxaliplatin and irinotecan unless contraindicated, refused or unavailable
- Progression after prior targeted treatment for CRC with actionable mutations such as EGFR, KRAS, BRAF and MSI- H/dMMR, if present.
- No more that 2 lines of cytotoxic chemotherapy for advanced or metastatic disease
- No more than 4 lines of systemic regimens for advanced or metastatic disease
- Participants must have at least one lesion that meets the definition of measurable disease by RECIST v1.1.
- +4 more criteria
You may not qualify if:
- Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures.
- Active brain metastases or leptomeningeal metastases.
- Prior stem cell, tissue, or solid organ transplant.
- Another malignancy that required treatment within the past 2 years, with the exception of those with a negligible risk of metastasis or death such as adequately treated non-melanomatous skin cancer, localized prostate cancer (Gleason Score \< 6), or carcinoma in situ.
- Active viral, bacterial, or fungal infection
- Prior treatment with ADAM9 targeted agent for cancer.
- Prior treatment with major surgery, mediastinal or lung radiation, vaccination with live virus vaccines, systemic cancer treatment, chimeric antigen receptor (CAR)-T cell therapy, or experimental treatment within 4 weeks of the start of study treatment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MacroGenicslead
Study Sites (7)
UCSF - Helen Diller Family Cancer Center
San Francisco, California, 94115, United States
Mass General Brigham
Boston, Massachusetts, 02114, United States
Dana Farber/Harvard Cancer Center
Boston, Massachusetts, 02115, United States
South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan, 49546, United States
Icahn School of Medicine at Mt. Sinai
New York, New York, 10029, United States
South Texas Accelerated Research Therapeutics (START) San Antonio
San Antonio, Texas, 78229, United States
South Texas Accelerated Research Therapeutics (START) Mountain Region
West Valley City, Utah, 84119, United States
Related Publications (1)
Scribner JA, Brown JG, Son T, Jin L, McKenzie C, Nam V, Bush C, Quinonez D, Ford D, Tamura J, Gorlatov S, Summers A, Hav M, Li H, Sharma NK, Zhang X, Diedrich G, Butler S, Bonvini E, Loo D. Preclinical Development of MGC028, an ADAM9-Targeted, Glycan-Linked, Exatecan-Based Antibody-Drug Conjugate for the Treatment of Solid Cancers. Mol Cancer Ther. 2026 Apr 2;25(4):517-528. doi: 10.1158/1535-7163.MCT-25-0461.
PMID: 41166694DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Pepi Pencheva, M.D.
MacroGenics
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 4, 2024
First Posted
December 9, 2024
Study Start
February 13, 2025
Primary Completion (Estimated)
November 1, 2026
Study Completion (Estimated)
April 1, 2027
Last Updated
April 27, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share