A Study Of MGC026 In Participants With Advanced Solid Tumors

Study Overview

A Study of MGC026 in Participants With Advanced Solid Tumors

The study is designed to understand the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of MGC026 in participants with relapsed or refractory, unresectable, locally advanced or metastatic solid tumors The study has a dose escalation portion and a cohort expansion portion of the study. Participants will receive MGC026 by intravenous (IV) infusion. The dose of MGC026 will be assigned at the time of enrollment. Participants may receive up to 35 treatments if there are no severe side effects and as long as the cancer does not get worse. Participants will be monitored for side effects, and progression of cancer, have blood samples collected for routing laboratory work, and blood samples collected for research purposes.

N/A

Advanced Solid Tumor
Advanced Cancer
Metastatic Cancer
Squamous Cell Carcinoma of Head and Neck
Non Small Cell Lung Cancer
Small-cell Lung Cancer
Bladder Cancer
Sarcoma
Endometrial Cancer
Melanoma
Castration Resistant Prostatic Cancer
Cervical Cancer
Colorectal Cancer
Gastric Cancer
Gastro-esophageal Cancer
Pancreas Cancer
Clear Cell Renal Cell Carcinoma
Hepatocellular Carcinoma
Platinum-resistant Ovarian Cancer
Breast Cancer
Ovarian Cancer
Esophageal Squamous Cell Cancer (SCC)

BIOLOGICAL: MGC026 Dose Escalation
BIOLOGICAL: MGC026 Dose for Expansion

CP-MGC026-01

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2024-01-12	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-08-11
First Submitted that Met QC Criteria 2024-02-01	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-08-14
First Posted (ACTUAL) 2024-02-05	Results First Posted N/A	Last Verified 2025-08

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Cohort 1 MGC026 is a topoisomerase 1 inhibitor (TOP1i)-based ADC that targets B7-H3 administered IV every 3 weeks.	BIOLOGICAL: MGC026 Dose Escalation Escalating doses of MGC026 BIOLOGICAL: MGC026 Dose for Expansion MGC026 recommended dose for expansion
EXPERIMENTAL: Cohort 2	BIOLOGICAL: MGC026 Dose Escalation Escalating doses of MGC026 BIOLOGICAL: MGC026 Dose for Expansion MGC026 recommended dose for expansion
EXPERIMENTAL: Cohort 3	BIOLOGICAL: MGC026 Dose Escalation Escalating doses of MGC026 BIOLOGICAL: MGC026 Dose for Expansion MGC026 recommended dose for expansion
EXPERIMENTAL: Cohort 4	BIOLOGICAL: MGC026 Dose Escalation Escalating doses of MGC026 BIOLOGICAL: MGC026 Dose for Expansion MGC026 recommended dose for expansion
EXPERIMENTAL: Cohort 5	BIOLOGICAL: MGC026 Dose Escalation Escalating doses of MGC026 BIOLOGICAL: MGC026 Dose for Expansion MGC026 recommended dose for expansion
EXPERIMENTAL: Cohort 6	BIOLOGICAL: MGC026 Dose Escalation Escalating doses of MGC026 BIOLOGICAL: MGC026 Dose for Expansion MGC026 recommended dose for expansion
EXPERIMENTAL: Expansion cohort 1	BIOLOGICAL: MGC026 Dose for Expansion MGC026 recommended dose for expansion
EXPERIMENTAL: Expansion cohort 2	BIOLOGICAL: MGC026 Dose for Expansion MGC026 recommended dose for expansion
EXPERIMENTAL: Expansion cohort 3	BIOLOGICAL: MGC026 Dose for Expansion MGC026 recommended dose for expansion
EXPERIMENTAL: Expansion cohort 4	BIOLOGICAL: MGC026 Dose for Expansion MGC026 recommended dose for expansion
EXPERIMENTAL: Expansion Cohort 5	BIOLOGICAL: MGC026 Dose for Expansion MGC026 recommended dose for expansion
EXPERIMENTAL: Expansion Cohort 6	BIOLOGICAL: MGC026 Dose for Expansion MGC026 recommended dose for expansion

Primary Outcome Measures	Measure Description	Time Frame
Number of participants with adverse events (AEs) and serious AEs (SAEs), AEs leading to dose delay, AEs leading to dose reduction, AEs leading to treatment discontinuations, AEs meeting criteria for dose limiting toxicity, and AEs or special interest.		Throughout the study, up to 135 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Overall response rate in advanced solid tumors	The objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) is used to estimate the proportion of participants in the Response Evaluable population who achieve best overall response of complete response (CR) or partial response (PR) (called responders). Complete response (CR) is defined as disappearance of all target and non-target lesions. Partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, no progression of non-target lesions, and no new lesions	Throughout the study, up to 135 weeks
Duration of response (DoR) in advanced solid tumors	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. (RECIST 1.1) is used to classify responses.	Throughout the study, up to 135 weeks
ORR rate in metastatic castration resistant prostate cancer (mCRPC)	The ORR per Prostate Cancer Working Group 3 (PCWG3) criteria is estimated as the proportion of participants in the Response Evaluable population who achieve best overall response of CR or PR (called responders).	Throughout the study, up to 135 weeks
DoR in mCRPC	DoR is defined as the time from the date of initial response (CR or PR) to the date of first documented progression, per PCWG3 criteria or death from any cause, whichever occurs first.	Throughout the study, up to 135 weeks
Mean (standard deviation [SD]) of MGC026 total and conjugated antibody maximum serum concentration (Cmax)	The maximum concentration in the bloodstream at the end of the infusion.	Cycle 1 Day 1: at baseline, end of infusion (EOI) approximately 1 hr, 4hrs after EOI, Day 2 and Day 4.
Mean (standard deviation [SD]) of MGC026 unconjugated payload Cmax	The maximum concentration in the bloodstream at the end of the infusion.	Cycle 1 Day 1: at baseline, end of infusion (EOI) approximately 1 hr, 4hrs after EOI, Day 2 and Day 4.
Mean (SD) of MGC026 total and conjugated antibody area under the time concentration curve (AUC)	Calculated exposure to MGC026	Cycle 1 Day 1: at baseline, EOI approximately 1 hr, 4hrs after EOI, Day 2, Day 4, Day 8, Day 15, and predose Cycle 2 Day 1
Mean (SD) of MGC026 unconjugated payload AUC	Calculated exposure to MGC026	Cycle 1 Day 1: at baseline, EOI approximately 1 hr, 4hrs after EOI, Day 2, Day 4, Day 8, Day 15, and predose Cycle 2 Day 1
Number of participants who develop anti-MGC026 antibodies (immunogenicity)	Development of anti-MGC026 antibodies in the bloodstream	Day 1, Day 15, and Day 1 of every 21-day cycle, throughout the study, average of 1 year.

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

Name: Global Trial Manager

Phone Number: 301-251-5172

Email: info@macrogenics.com

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Adults ≥ 18 years old, able to provide informed consent
Adequate performance and laboratory parameters
Availability of archival or formalin-fixed paraffin-embedded tumor tissue sample. Participants may undergo a fresh tumor biopsy to obtain a specimen for testing if an archival tumor sample is not available. Participants with no available archival tissue sample who cannot safely undergo a fresh biopsy as determined by consultation between the sponsor and investigator are eligible
Unresectable, locally advanced or metastatic solid tumors including: squamous cell cancer (SCC) of the head and neck, esophageal SCC, squamous and non-squamous non-small cell lung cancer, small cell lung cancer, bladder cancer, sarcoma, endometrial cancer, melanoma, castration resistant prostate cancer, breast cancer, ovarian cancer, cervical cancer, colorectal cancer gastric or gastroesophageal cancer, pancreatic carcinoma, clear cell renal cell cancer or hepatocellular cancer.
Measurable disease per RECIST v1.1. Participants with metastatic CRPC without measurable disease are eligible.
Must be willing to use highly effective methods of birth control from the time of consent through 7 months after discontinuation of MGC026.
Not pregnant or breastfeeding.

Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures.
Another cancer that required treatment within the past 2 years, with the exception of those with low risk of cancer spreading or death such as adequately treated non melanomatous skin cancer, localized prostate cancer (Gleason Score < 6), or carcinoma in situ.
Patients with history of prior central nervous system (CNS) metastasis must have been treated, be asymptomatic, and not have concurrent treatment for CNS disease, progression of CNS metastases on magnetic resonance imaging, computed tomography or positron emission tomography, or history of leptomeningeal disease or cord compression at the time of enrollment.
Treatment with surgery, systemic cancer therapy, immunotherapy, chimeric antigen receptor-T therapy, or anti-hormonal within protocol specified intervals.
Prior treatment with any B7-H3 targeted agent for cancer or any ADC with a topoisomerase payload.
Prior autologous or allogeneic stem cell or solid organ transplant.
Clinically significant cardiovascular, pulmonary, or gastrointestinal disorders.
Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 1 week of first study drug administration.
Known history of hepatitis B or C infection or known positive test for hepatitis B surface antigen or core antigen, or hepatitis C polymerase chain reaction.
Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
History of primary immunodeficiency.
Major trauma or major surgery within 4 weeks of first study drug administration.
Known hypersensitivity to recombinant proteins.

Collaborators and Investigators

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

Investigators

STUDY_DIRECTOR: Denise Casey, MD, MacroGenics

Publications

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

General Publications

No publications available

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