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Trial record 1 of 1 for:    NCT03729596
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MGC018 With or Without MGA012 in Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03729596
Recruitment Status : Recruiting
First Posted : November 2, 2018
Last Update Posted : March 27, 2020
Sponsor:
Information provided by (Responsible Party):
MacroGenics

Tracking Information
First Submitted Date  ICMJE October 30, 2018
First Posted Date  ICMJE November 2, 2018
Last Update Posted Date March 27, 2020
Actual Study Start Date  ICMJE November 21, 2018
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 31, 2018)
  • 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.
  • Maximum Tolerated Dose [ Time Frame: up to 42 days from first dose ]
    Maximum tolerated or maximum administered dose of MGC018 and MGC018 + MGA012
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2018)
  • Area under the curve [ Time Frame: 24 months ]
    Area under the plasma concentration versus time curve of MGC018 and MGC018+MGA012
  • Cmax [ Time Frame: 24 months ]
    Maximum Plasma Concentration of MGC018 and MGC018+MGA012
  • Tmax [ Time Frame: 24 months ]
    Time to reach maximum (peak) plasma concentration of MGC018 and MGC018+MGA012
  • Ctrough [ Time Frame: 24 months ]
    Trough plasma concentration of MGC018 and MGC018+MGA012
  • CL [ Time Frame: 24 months ]
    Total body clearance of the drug from plasma of MGC018 and MGC018+MGA012
  • Vss [ Time Frame: 24 months ]
    Apparent volume of distribution at steady state of MGC018 and MGC018+MGA012
  • t1/2 [ Time Frame: 24 months ]
    Terminal half life of MGC018 and MGC018+MGA012
  • Percent of patients with anti-drug antibodies against MGC018 and MGA012 [ Time Frame: 24 months ]
    immunogenicity
  • Preliminary anti-tumor activity of MGC018 and MGC018+MGA012 [ Time Frame: 24 months ]
    Efficacy assessed as best overall response rate using both conventional Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) (Appendix 5) and immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MGC018 With or Without MGA012 in Advanced Solid Tumors
Official Title  ICMJE 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
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.
Detailed Description This Phase 1/2, bifurcated-design study will characterize safety, dose-limiting toxicities (DLTs), and maximum tolerated/administered dose (MTD/MAD) for MGC018 as monotherapy (Module A) or in combination with MGA012 (Module B) in patients with advanced solid tumors. Module B will commence after the MTD/MAD of MGC018 monotherapy is defined. Each module consists of a Dose Escalation (3+3+3 design) followed by a Cohort Expansion Phase. Patients with solid tumors of any histology will be enrolled in the Dose Escalation Phases; Cohort Expansion will include disease-specific cohorts. Patients who do not experience DLT/unacceptable toxicity or meet criteria for permanent discontinuation may undergo additional cycles. Patients will be followed for survival every 3 months for 2 years following last dose.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Following monotherapy dose escalation, MGC018 will be evaluated in combination with MGC018. Dose escalation will also proceed using a 3+3+3 design to identify an MTD for the combination, and will then be followed by a Cohort Expansion for the combination.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor, Adult
Intervention  ICMJE
  • Biological: MGC018
    Anti-B7-H3 antibody drug conjugate
  • Biological: MGA012
    Anti-PD-1 antibody
    Other Name: INCMGA00012
Study Arms  ICMJE
  • Experimental: MGC018 Monotherapy
    MGC018: Anti-B7-H3 antibody drug conjugate
    Intervention: Biological: MGC018
  • Experimental: MGC018 plus MGA012
    MGC018: Anti-B7-H3 antibody drug conjugate; MGA012: Anti-PD-1 antibody
    Interventions:
    • Biological: MGC018
    • Biological: MGA012
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 31, 2018)
193
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2025
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Tissue specimen available for retrospective analysis of B7-H3 and PD-L1 expression.
  • Eastern Cooperative Oncology Group performance status of 0 or 1
  • Life expectancy ≥ 12 weeks
  • Measurable disease
  • Dose Escalation Phase: Patients with histologically proven, unresectable, locally advanced or metastatic solid tumors for whom no approved therapy with demonstrated clinical benefit is available. For all tumor types, the requirement for previous systemic therapy may be waived if a patient was intolerant of or refused standard therapy.
  • Cohort Expansion Phase: Disease-specific prior therapy requirements to be specified.
  • Acceptable laboratory parameters and adequate organ reserve.
  • Patients with prior immune checkpoint inhibitors must have related toxicities reduced to Grade 0, 1, or baseline, with the exception of well-controlled hypothyroidism.

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 or CT for at least 21 days after last day of prior therapy for the CNS metastases, or concurrent leptomeningeal disease or cord compression at the time of enrollment.
  • History of autoimmune disease with certain exceptions such as vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic therapy within the past 2 years, patients with history of Grave's disease that are now euthyroid clinically and by lab testing.
  • Patients who experienced the following immune checkpoint inhibitor-related AEs make the patient ineligible despite the AE resolving to ≤ Grade 1 or baseline: ≥ Grade 3 ocular AE, neurologic toxicity, colitis, pneumonitis, renal toxicity; changes in liver function tests that met criteria for Hy's Law.
  • Prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents for cancer.
  • Treatment with systemic cancer therapy within 3 weeks, investigational therapy within 4 weeks; radiation within 2 weeks; corticosteroids (greater than or equal to 10 mg prednisone or equivalent per day) or other immune suppressive drugs within 2 weeks of first study drug administration.
  • Clinically significant cardiovascular disease.
  • Clinically significant pulmonary compromise or requirement for supplemental oxygen.
  • History of clinically-significant cardiovascular disease.
  • Active viral, 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.
  • History of allogeneic bone marrow, stem cell, or solid organ transplant.
  • Trauma or major surgery within 4 weeks of first study drug administration.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Joanna Lohr, PhD (240) 552-8030 lohrj@macrogenics.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03729596
Other Study ID Numbers  ICMJE CP-MGC018-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party MacroGenics
Study Sponsor  ICMJE MacroGenics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Chet Bohac, PharmD, MD, MSc MacroGenics
PRS Account MacroGenics
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP