A Study of MGC028 in Participants With Advanced Solid Tumors

April 23, 2026 updated by: MacroGenics

A Phase 1, First-in-Human, Open Label, Dose Escalation and Cohort Expansion Study of MGC028 in Participants With Advanced Solid Tumors

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

124

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • Recruiting
        • UCSF - Helen Diller Family Cancer Center
        • Principal Investigator:
          • Pamela Munster
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Mass General Brigham
        • Principal Investigator:
          • Harshaband Singh
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Dana Farber/Harvard Cancer Center
        • Principal Investigator:
          • Kimberly Perez
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • South Texas Accelerated Research Therapeutics (START) Midwest
        • Principal Investigator:
          • Manish Sharma
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mt. Sinai
        • Principal Investigator:
          • Deborah Doroshow
    • Texas
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • South Texas Accelerated Research Therapeutics (START) San Antonio
        • Principal Investigator:
          • Drew Rasco
    • Utah
      • West Valley City, Utah, United States, 84119
        • Recruiting
        • South Texas Accelerated Research Therapeutics (START) Mountain Region
        • Principal Investigator:
          • Justin Call

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.
  • Participants must have an available archival or formalin-fixed paraffin-embedded tumor tissue or be willing to undergo a biopsy procedure to obtain a fresh tumor sample.
  • Participants have acceptable physical condition and laboratory values.
  • Participants of childbearing potential must agree to use highly effective methods of birth control.
  • Participants must not be pregnant, planning to be 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
Dose level 1 of MGC028, IV
Biological: MGC028
MGC028 is an antibody-drug conjugate targeted against ADAM9.
Experimental: Cohort 2
Dose level 2 of MGC028, IV
Biological: MGC028
MGC028 is an antibody-drug conjugate targeted against ADAM9.
Experimental: Cohort 3
Dose level 3 of MGC028, IV
Biological: MGC028
MGC028 is an antibody-drug conjugate targeted against ADAM9.
Experimental: Cohort 4
Dose level 4 of MGC028, IV
Biological: MGC028
MGC028 is an antibody-drug conjugate targeted against ADAM9.
Experimental: Cohort 5
Dose level 5 of MGC028, IV
Biological: MGC028
MGC028 is an antibody-drug conjugate targeted against ADAM9.
Experimental: Cohort 6
Dose level 6 of MGC028, IV
Biological: MGC028
MGC028 is an antibody-drug conjugate targeted against ADAM9.
Experimental: Expansion Cohort 1
MTD or MAD of MGC028, IV
Biological: MGC028
MGC028 is an antibody-drug conjugate targeted against ADAM9.
Experimental: Expansion Cohort 2
MTD or MAD of MGC028, IV
Biological: MGC028
MGC028 is an antibody-drug conjugate targeted against ADAM9.
Experimental: Expansion Cohort 3
MTD or MAD of MGC028, IV
Biological: MGC028
MGC028 is an antibody-drug conjugate targeted against ADAM9.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number and Types of Adverse Events (AEs) in Participants Receiving MGC028
Time Frame: Throughout the study treatment and safety follow up period, up to 25 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Develop Anti-Drug Antibodies to MGC028
Time Frame: Throughout the study treatment period, up to 2 years
Throughout the study treatment period, up to 2 years
Objective Response Rate (ORR)
Time Frame: Throughout the study and follow up period, up to 2.5 years.
The ORR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is estimated as the proportion of participants in the Response Evaluable Population who achieve Best Overall Response of Complete Response or Partial Response.
Throughout the study and follow up period, up to 2.5 years.
Median Duration of Response
Time Frame: Throughout the study and follow up period, up to 2.5 years.
DoR is defined as the time from the date of initial response (CR or PR) to the date of first documented progression or death from any cause, whichever occurs first.
Throughout the study and follow up period, up to 2.5 years.
Mean maximum concentration of MGC028 antibody
Time Frame: Through Cycle 6 of the study, approximately 18 weeks
Measurement of the highest concentration of MGC028 conjugated and total antibody in the bloodstream.
Through Cycle 6 of the study, approximately 18 weeks
Mean Area Under the Concentration Time Curve of MGC028 antibody
Time Frame: Through Cycle 6 of the study, approximately 18 weeks
Measurement of the total exposure of MGC028 conjugated and total antibody in the bloodstream.
Through Cycle 6 of the study, approximately 18 weeks
Mean maximum concentration of MGC028 free payload
Time Frame: Through Cycle 6 of the study, approximately 18 weeks
Measurement of the highest concentration of MGC028 free payload in the bloodstream.
Through Cycle 6 of the study, approximately 18 weeks
Mean Area Under the Concentration Time Curve Total exposure of MGC028 payload
Time Frame: Through Cycle 6 of the study, approximately 18 weeks
Measurement of the total exposure of MGC028 free payload in the bloodstream
Through Cycle 6 of the study, approximately 18 weeks
Change from baseline in the level of ADAM9 expression in tumor specimens, using immunohistochemistry
Time Frame: Baseline and approximately 28 days after the first dose of MGC028.
Baseline and approximately 28 days after the first dose of MGC028.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MacroGenics

Investigators

  • Study Director: Pepi Pencheva, M.D., MacroGenics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 13, 2025

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

December 4, 2024

First Submitted That Met QC Criteria

December 4, 2024

First Posted (Actual)

December 9, 2024

Study Record Updates

Last Update Posted (Actual)

April 27, 2026

Last Update Submitted That Met QC Criteria

April 23, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CP-MGC028-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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