A Study of MGC028 in Participants With Advanced Solid Tumors

Official title

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

Overview

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.

Interventions

• Biological MGC028
  MGC028 is an antibody-drug conjugate targeted against ADAM9.

Primary outcome measures

• 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]

Secondary outcome measures (8)

• Mean maximum concentration of MGC028 antibody [Time frame: 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]
• 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) [Time frame: 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.]
• Mean maximum concentration of MGC028 free payload [Time frame: 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]
• 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.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• UCSF - Helen Diller Family Cancer Center — San Francisco
• Mass General Brigham — Boston
• Dana Farber/Harvard Cancer Center — Boston
• South Texas Accelerated Research Therapeutics (START) Midwest — Grand Rapids
• Icahn School of Medicine at Mt. Sinai — New York
• South Texas Accelerated Research Therapeutics (START) San Antonio — San Antonio
• South Texas Accelerated Research Therapeutics (START) Mountain Region — West Valley City

Publications

• 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. PMID 41166694

Identifiers

NCT: NCT06723236 · CP-MGC028-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗