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MGC018 With or Without MGA012 in Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03729596
Recruitment Status : Recruiting
First Posted : November 2, 2018
Last Update Posted : December 16, 2020
Sponsor:
Information provided by (Responsible Party):
MacroGenics

Brief Summary:
The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of MGC018 administered alone and in combination with MGA012 in patients with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor, Adult Metastatic Castrate Resistant Prostate Cancer Non Small Cell Lung Cancer Triple Negative Breast Cancer Biological: MGC018 Biological: MGA012 Phase 1 Phase 2

Detailed Description:

This Phase 1/2 study will characterize safety, dose-limiting toxicities (DLTs), and maximum tolerated/administered dose (MTD/MAD) and anti-tumor activity for MGC018 as monotherapy (Module A) in patients with advanced solid tumors. Each module consists of a Dose Escalation (3+3+3 design) followed by a Cohort Expansion Phase. 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), and triple-negative breast cancer (TNBC). 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.

Module B, MGC018 in combination with MGA012, Dose Escalation and Cohort Expansion will commence only upon sponsor notification to all study investigators.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation will use a 3+3+3 design to identify an MAD or MTD, followed by a Cohort Expansion.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of MGC018 (Anti-B7-H3 Antibody Drug Conjugate) Alone and in Combination With MGA012 (Anti-PD-1 Antibody) in Patients With Advanced Solid Tumors
Actual Study Start Date : November 21, 2018
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : May 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MGC018 Monotherapy
MGC018: Anti-B7-H3 antibody drug conjugate
Biological: MGC018
Anti-B7-H3 antibody drug conjugate

Experimental: MGC018 plus MGA012
MGC018: Anti-B7-H3 antibody drug conjugate; MGA012: Anti-PD-1 antibody
Biological: MGC018
Anti-B7-H3 antibody drug conjugate

Biological: MGA012
Anti-PD-1 antibody
Other Name: INCMGA00012




Primary Outcome Measures :
  1. Incidence of Adverse Events of MGC018 and MGC018 + MGA012 as assessed by CTCAE v4.03 [ Time Frame: 30 days after last dose ]
    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.

  2. Maximum Tolerated Dose [ Time Frame: up to 42 days from first dose ]
    Maximum tolerated or maximum administered dose of MGC018 and MGC018 + MGA012


Secondary Outcome Measures :
  1. Preliminary anti-tumor activity of MGC018 and MGC018+MGA012 [ Time Frame: 24 months ]
    Efficacy assessed as best overall response rate using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

  2. PSA response rate [ Time Frame: 24 months ]
    Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA)

  3. Radiographic progression-free survival [ Time Frame: 24 months ]
    For prostate cancer patients, time from first dose to first radiographic progression in soft tissue or bone, or death from any cause

  4. Patient-reported Outcome [ Time Frame: 24 months ]
    For prostate cancer patients, change from baseline in pain intensity as measured by the Brief Pain Inventory-Short Form scale

  5. Area under the curve [ Time Frame: 24 months ]
    Area under the plasma concentration versus time curve of MGC018 and MGC018+MGA012

  6. Cmax [ Time Frame: 24 months ]
    Maximum Plasma Concentration of MGC018 and MGC018+MGA012

  7. Tmax [ Time Frame: 24 months ]
    Time to reach maximum (peak) plasma concentration of MGC018 and MGC018+MGA012

  8. Ctrough [ Time Frame: 24 months ]
    Trough plasma concentration of MGC018 and MGC018+MGA012

  9. CL [ Time Frame: 24 months ]
    Total body clearance of the drug from plasma of MGC018 and MGC018+MGA012

  10. Vss [ Time Frame: 24 months ]
    Apparent volume of distribution at steady state of MGC018 and MGC018+MGA012

  11. t1/2 [ Time Frame: 24 months ]
    Terminal half life of MGC018 and MGC018+MGA012

  12. Immunogenicity [ Time Frame: 24 months ]
    Percent of patients with anti-drug antibodies against MGC018 and MGA012



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03729596


Contacts
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Contact: Joanna Lohr, PhD (240) 552-8030 lohrj@macrogenics.com

Locations
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United States, California
UCLA Department of Medicine - Hematology/Oncology Recruiting
Santa Monica, California, United States, 90404
Contact: Kathryn Hilburn, RN    310-633-8400    khilburn@mednet.ucla.edu   
Principal Investigator: John Shen, MD         
United States, Maryland
The Johns Hopkins Kimmel Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Sin Chan, MS    410-614-3630    schan33@jhmi.edu   
Principal Investigator: Eugene Shenderov, MD, PhD         
United States, Michigan
START Midwest Active, not recruiting
Grand Rapids, Michigan, United States, 49546
United States, North Carolina
Carolina Biooncology Institute Recruiting
Huntersville, North Carolina, United States, 28078
Contact: Jaelyn Rose Linski, MA    704-947-6599 ext 111    jlinski@carolinabiooncology.org   
Principal Investigator: John Powderly, MD         
United States, Virginia
Inova Schar Cancer Institute Recruiting
Fairfax, Virginia, United States, 22031
Contact: Kelly Jeffords       Kelly.jeffords@inova.org   
Principal Investigator: Sekwon Jang, MD         
Virginia Cancer Specialist Recruiting
Fairfax, Virginia, United States, 22031
Contact: Claudia Philips    703-208-9268    claudia.phillips@usoncology.com   
Principal Investigator: Alexander Spira, MD         
Australia
St Vincent's Health Network (Kinghorn Cancer Centre) Recruiting
Darlinghurst, Australia, 2010
Contact: Ashley Douglas    +61 2 9355 5618    Ashley.Douglas@svha.org.au   
Principal Investigator: Anthony Joshua         
Austin Health - Olivia Newton John Cancer Center Recruiting
Heidelberg, Australia, 3084
Contact: Naila Pachani    +61 3 9496 9118    naila.pachani@austin.org.au   
Principal Investigator: Andrew Weickhardt, MD         
Calvary Mater NewCastle Recruiting
Waratah, Australia, 2298
Contact: Kerrie Cornall    +61 2 4014 3280    kerrie.cornall@calvarymater.org.au   
Principal Investigator: Girish Mallesara, MD         
The University of Queensland - Princess Alexandra Hospital (PAH) Not yet recruiting
Woolloongabba, Australia, 4105
Contact: Wangyi Jiang    +61 7 3176 8295    Wangyi.Juang@health.qld.gov.au   
Principal Investigator: Wen Xu         
Poland
Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie Oddział Kliniczny Onkologii Recruiting
Krakow, Poland, 31-501
Contact: Piotr Wysocki    48 12 424 89 12    piotr.wysocki@uj.edu.pl   
Principal Investigator: Piotr Wysocki         
Med-Polonia Sp. z o.o. Recruiting
Poznań, Poland, 60-693
Contact: Rodryg Ramlau    48505758992    rramlau@gmail.com   
Principal Investigator: Rodryg Ramlau         
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Oddział Badań Wczesnych Faz Recruiting
Warsaw, Poland, 02-781
Contact: Joanna Dylewska-Rzeznik    48 22 546 26 94    Joanna.Dylewska-Rzeznik@pib-nio.pl   
Principal Investigator: Iwona Lugowska         
Magodent Sp. z o.o. Szpital Elbląska Oddział Onkologii Klinicznej/ Chemioterapii Recruiting
Warszawa, Poland, 01-748
Contact: Jakub Żołnierek    48 22 430 88 50    qbazolnier@wp.pl   
Principal Investigator: Jakub Żołnierek         
Sponsors and Collaborators
MacroGenics
Investigators
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Study Director: Chet Bohac, PharmD MD MSc MacroGenics
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Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT03729596    
Other Study ID Numbers: CP-MGC018-01
First Posted: November 2, 2018    Key Record Dates
Last Update Posted: December 16, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MacroGenics:
antibody-drug conjugate (ADC)
B7-H3
Prostate cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Triple Negative Breast Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Breast Neoplasms
Breast Diseases
Skin Diseases