MGC018 With or Without MGA012 in Advanced Solid Tumors

NCT03729596 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: CP-MGC018-01
• Study Type: interventional
• Target: 143
• Locations: 4 countries
• Sites: 21

Brief Summary

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of vobramitamab duocarmazine (MGC018) in patients with advanced solid tumors. Patients with solid tumors will be enrolled in the Dose Escalation Phase; Cohort Expansion will include metastatic castrate-resistant prostate cancer (mCRPC), non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), squamous cell carcinoma of the head and neck (SCCHN), and melanoma. Patients who do not experience unacceptable toxicity or meet criteria for permanent discontinuation may undergo additional cycles for up to two years. Patients in Cohort Expansion will be followed for survival every 3 months for 2 years following last dose.

Conditions

Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Cancer; Melanoma; Advanced Solid Tumor, Adult; Metastatic Castrate Resistant Prostate Cancer; Non Small Cell Lung Cancer

Keywords

antibody-drug conjugate (ADC); B7-H3

Outcome Measures

Primary Outcomes (2)

• Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03

  Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.

  Throughout the study up to 24 months

• Number of Participants With Dose Limiting Toxicities (DLT)

  Number of participants with severe side effects from study treatment during the DLT evaluation period (6 weels)

  up to 42 days from first dose

Secondary Outcomes (14)

• Best Overall Response (BOR) of Vobramitamab Duocarmazine

  Throughout the study for up to 24 months

• Objective Response Rate (ORR) of Vobramitamab Duocarmazine

  Efficacy evaluations every 9 weeks throughout the study for up to 24 months

• Progression Free Survival (PFS) of Vobramitamab Duocarmazine

  Every 9 weeks for up to 24 months

• Median Duration of Response (DoR) of Vobramitamab Duocarmazine

  Throughout the study for up to 48 months

• Median Overall Survival (OS) of Vobramitamab Duocarmazine

  Every 9 weeks for up to 24 months

Study Arms (10)

Cohort 1

EXPERIMENTAL

0.5 mg/kg IV every 3 weeks

Biological: vobramitamab duocarmazine

Cohort 2

EXPERIMENTAL

1.0 mg/kg IV every 3 weeks

Biological: vobramitamab duocarmazine

Cohort 3

EXPERIMENTAL

2.0 mg/kg IV every 3 weeks

Biological: vobramitamab duocarmazine

Cohort 4

EXPERIMENTAL

3.0 mg/kg IV every 3 weeks

Biological: vobramitamab duocarmazine

Cohort 5

EXPERIMENTAL

4.0 mg/kg IV every 3 weeks

Biological: vobramitamab duocarmazine

mCRPC expansion

EXPERIMENTAL

3.0 mg/kg IV every 3 weeks

Biological: vobramitamab duocarmazine

NSCLC expansion

EXPERIMENTAL

3.0 mg/kg IV every 3 weeks

Biological: vobramitamab duocarmazine

TNBC expansion

EXPERIMENTAL

3.0 mg/kg IV every 3 weeks

Biological: vobramitamab duocarmazine

Melanoma expansion

EXPERIMENTAL

3.0 mg/kg IV every 3 weeks

Biological: vobramitamab duocarmazine

SCCHN expansion

EXPERIMENTAL

3.0 mg/kg IV every 3 weeks

Biological: vobramitamab duocarmazine

Interventions

vobramitamab duocarmazine BIOLOGICAL

Anti-B7H3 antibody drug conjugate

Also known as: MGC018

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Melanoma expansion; NSCLC expansion; SCCHN expansion; TNBC expansion; mCRPC expansion

Eligibility Criteria

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

You may qualify if:

• Tissue specimen available for retrospective analysis of B7-H3 and PD-L1 expression.
• Eastern Cooperative Oncology Group performance status of ≤2
• Life expectancy ≥ 12 weeks for dose escalation phase and ≥ 24 weeks for cohort expansion phase
• Measurable disease. Prostate cancer patients with bone only disease are eligible.
• Acceptable laboratory parameters and adequate organ reserve.
• Dose Escalation Phase: Patients with histologically proven, unresectable, locally advanced or metastatic solid tumors for whom no therapy with demonstrated clinical benefit is available.
• Module A Cohort Expansion:
• mCRPC that has progressed with one prior line of chemotherapy for metastatic disease and no more than two prior lines of anti-hormonal therapy.
• NSCLC: metastatic disease after standard cytotoxic, targeted, and biologic or checkpoint inhibitor therapy. No more than 2 prior lines of chemotherapy.
• TNBC: Locally advance or metastatic disease that has progressed following at least one systemic therapy.
• SCCHN that has progressed during or following at least one systemic therapy for metastatic or recurrent unresectable disease. No more than 2 prior lines of chemotherapy.
• Melanoma that has progressed during or following at least one systemic treatment for unresectable locally advanced or metastatic disease. Patients who are intolerant of or refused standard therapy are eligible.

You may not qualify if:

• 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 MRI, CT or PET within 6 months, or history of leptomeningeal disease or cord compression at the time of enrollment.
• Prior treatment with B7-H3 targeted agents for cancer.
• Treatment with systemic cancer therapy, biologic agents, or anti-hormonal therapy (mCRPC) within 4 weeks, prior small molecule targeted or kinase inhibitors within 14 days or 5 half-lives, prior radioligand within 6 months
• Clinically significant cardiovascular disease.
• Clinically significant pulmonary compromise or requirement for supplemental oxygen.
• History of clinically-significant cardiovascular disease, including but not limited to pericarditis or pericardial effusion.
• Active viral (including confirmed or presumed COVID-19), bacterial, or systemic fungal infection requiring parenteral treatment within 7 days 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.
• Major trauma or major surgery within 4 weeks of first study drug administration.
• Clinically significant venous insufficiency.
• \> Grade 1 peripheral neuropathy.
• Evidence of pleural effusion.
• Evidence of ascites.
• Serum testosterone \>50 ng/dl or \>1.7 nmol/L in mCRPC in Module A Cohort Expansion Phase

Sponsors & Collaborators

• MacroGenics: lead

Study Sites (21)

UCLA Department of Medicine - Hematology/Oncology

Santa Monica, California, 90404, United States

Location

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

The Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, 21231, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Carolina Biooncology Institute

Huntersville, North Carolina, 28078, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

Virginia Cancer Specialist

Fairfax, Virginia, 22031, United States

Location

St Vincent's Health Network (Kinghorn Cancer Centre)

Darlinghurst, 2010, Australia

Location

Austin Health - Olivia Newton John Cancer Center

Heidelberg, 3084, Australia

Location

Calvary Mater NewCastle

Waratah, 2298, Australia

Location

The University of Queensland - Princess Alexandra Hospital (PAH)

Woolloongabba, 4105, Australia

Location

Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie Oddział Kliniczny Onkologii

Krakow, 31-501, Poland

Location

Med-Polonia Sp. z o.o.

Poznan, 60-693, Poland

Location

Magodent Sp. z o.o. Szpital Elbląska Oddział Onkologii Klinicznej/ Chemioterapii

Warsaw, 01-748, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Oddział Badań Wczesnych Faz

Warsaw, 02-781, Poland

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Institut Català D'Oncologia - Hospital Universitari Germans Trias I Pujol

Barcelona, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 20850, Spain

Location

Hospital Ruber Internacional

Madrid, 28034, Spain

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms; Melanoma; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Stephen L. Eck, MD
• Organization: MacroGenics, Inc.

info@macrogenics.com

301-251-5172

Study Officials

• Ashley Ward, M.D.

  MacroGenics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation will use a 3+3+3 design to identify an MAD or MTD, followed by a Cohort Expansion.

Study Record Dates

• First Submitted: October 30, 2018
• First Posted: November 2, 2018
• Study Start: November 21, 2018
• Primary Completion: March 18, 2023
• Study Completion: March 18, 2023
• Last Updated: July 31, 2025
• Results First Posted: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); ES (4); PL (4); US (9)