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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
124
MGC028 is an antibody-drug conjugate targeted against ADAM9.
UCSF - Helen Diller Family Cancer Center
San Francisco, California, United States
RECRUITINGDana Farber/Harvard Cancer Center
Boston, Massachusetts, United States
RECRUITINGSouth Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan, United States
RECRUITINGIcahn School of Medicine at Mt. Sinai
New York, New York, United States
RECRUITINGSouth Texas Accelerated Research Therapeutics (START) San Antonio
San Antonio, Texas, United States
RECRUITINGSouth Texas Accelerated Research Therapeutics (START) Mountain Region
West Valley City, Utah, United States
RECRUITINGNumber 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
Time frame: Throughout the study treatment and safety follow up period, up to 25 months
Mean maximum concentration of MGC028 antibody
Measurement of the highest concentration of MGC028 conjugated and total antibody in the bloodstream.
Time frame: Through Cycle 6 of the study, approximately 18 weeks
Mean Area Under the Concentration Time Curve of MGC028 antibody
Measurement of the total exposure of MGC028 conjugated and total antibody in the bloodstream.
Time frame: Through Cycle 6 of the study, approximately 18 weeks
Number of Participants Who Develop Anti-Drug Antibodies to MGC028
Time frame: Throughout the study treatment period, up to 2 years
Objective Response Rate (ORR)
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.
Time frame: Throughout the study and follow up period, up to 2.5 years.
Median Duration of Response
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.
Time frame: Throughout the study and follow up period, up to 2.5 years.
Mean maximum concentration of MGC028 free payload
Measurement of the highest concentration of MGC028 free payload in the bloodstream.
Time frame: Through Cycle 6 of the study, approximately 18 weeks
Mean Area Under the Concentration Time Curve Total exposure of MGC028 payload
Measurement of the total exposure of MGC028 free payload in the bloodstream
Time frame: 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.
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