A Study of MGC026 in Participants With Advanced Solid Tumors

NCT06242470 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CP-MGC026-01
• Study Type: interventional
• Target: 250
• Locations: 3 countries
• Sites: 12

Brief Summary

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.

Conditions

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)

Outcome Measures

Primary Outcomes (1)

• 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 of special interest.

  Throughout the study, up to 135 weeks

Secondary Outcomes (9)

• Overall response rate in advanced solid tumors

  Throughout the study, up to 135 weeks

• Duration of response (DoR) in advanced solid tumors

  Throughout the study, up to 135 weeks

• ORR rate in metastatic castration resistant prostate cancer (mCRPC)

  Throughout the study, up to 135 weeks

• DoR in mCRPC

  Throughout the study, up to 135 weeks

• Mean (standard deviation [SD]) of MGC026 total and conjugated antibody maximum serum concentration (Cmax)

  Cycle 1 Day 1: at baseline, end of infusion (EOI) approximately 1 hr, 4hrs after EOI, Day 2 and Day 4.

Study Arms (12)

Cohort 1

EXPERIMENTAL

MGC026 is a topoisomerase 1 inhibitor (TOP1i)-based ADC that targets B7-H3 administered IV every 3 weeks.

Biological: MGC026 Dose Escalation

Cohort 2

EXPERIMENTAL

Biological: MGC026 Dose Escalation

Cohort 3

EXPERIMENTAL

Biological: MGC026 Dose Escalation

Cohort 4

EXPERIMENTAL

Biological: MGC026 Dose Escalation

Cohort 5

EXPERIMENTAL

Biological: MGC026 Dose Escalation

Cohort 6

EXPERIMENTAL

Biological: MGC026 Dose Escalation

Expansion cohort 1

EXPERIMENTAL

Biological: MGC026 Dose for Expansion

Expansion cohort 2

EXPERIMENTAL

Biological: MGC026 Dose for Expansion

Expansion cohort 3

EXPERIMENTAL

Biological: MGC026 Dose for Expansion

Expansion cohort 4

EXPERIMENTAL

Biological: MGC026 Dose for Expansion

Expansion Cohort 5

EXPERIMENTAL

Biological: MGC026 Dose for Expansion

Expansion Cohort 6

EXPERIMENTAL

Biological: MGC026 Dose for Expansion

Interventions

MGC026 Dose Escalation BIOLOGICAL

Escalating doses of MGC026

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6

MGC026 Dose for Expansion BIOLOGICAL

MGC026 recommended dose for expansion

Expansion Cohort 5; Expansion Cohort 6; Expansion cohort 1; Expansion cohort 2; Expansion cohort 3; Expansion cohort 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

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.
• 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.

Sponsors & Collaborators

• MacroGenics: lead

Study Sites (12)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

RECRUITING

START Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

START-New York Long Island

Lake Success, New York, 11042, United States

RECRUITING

Providence Cancer Institute

Portland, Oregon, 97213, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

START Mountain Region

West Valley City, Utah, 84119, United States

RECRUITING

ICON Cancer Centre Wesley

Auchenflower, Queensland, 4066, Australia

RECRUITING

ICON Cancer Centre Kurralta Park

Kurralta Park, South Australia, 5037, Australia

RECRUITING

Austin Health- Olivia Newton John Cancer Center

Heidelberg, Victoria, 3084, Australia

RECRUITING

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 9DU, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust

Sutton, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Urinary Bladder Neoplasms; Sarcoma; Endometrial Neoplasms; Melanoma; Prostatic Neoplasms, Castration-Resistant; Uterine Cervical Neoplasms; Colorectal Neoplasms; Stomach Neoplasms; Pancreatic Neoplasms; Carcinoma, Renal Cell; Carcinoma, Hepatocellular; Breast Neoplasms; Ovarian Neoplasms; Esophageal Squamous Cell Carcinoma

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms, Connective and Soft Tissue; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Genital Diseases, Female; Genital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Prostatic Neoplasms; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Uterine Cervical Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Adenocarcinoma; Kidney Neoplasms; Kidney Diseases; Liver Neoplasms; Liver Diseases; Breast Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Neoplasms, Squamous Cell; Esophageal Neoplasms; Esophageal Diseases

Study Officials

• Denise Casey, MD

  MacroGenics

  STUDY DIRECTOR

Central Study Contacts

Global Trial Manager

CONTACT

301-251-5172; info@macrogenics.com

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: January 12, 2024
• First Posted: February 5, 2024
• Study Start: March 6, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); GB (2); US (7)