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MGC018 With or Without MGA012 in Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03729596
Recruitment Status : Not yet recruiting
First Posted : November 2, 2018
Last Update Posted : November 2, 2018
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
Solid Tumor, Adult Biological: MGC018 Biological: MGA012 Phase 1 Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 193 participants
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
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
Estimated Study Start Date : November 2018
Estimated Primary Completion Date : August 2020
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. Area under the curve [ Time Frame: 24 months ]
    Area under the plasma concentration versus time curve of MGC018 and MGC018+MGA012

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

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

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

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

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

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

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

  9. 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)



Information from the National Library of Medicine

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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 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 as described below. 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.

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

Locations
United States, Michigan
START Midwest Not yet recruiting
Grand Rapids, Michigan, United States, 49546
Contact: Kathy Estkowski    616-954-5551    kathy.estkowski@startmidwest.com   
Principal Investigator: Manish Sharma, MD         
United States, North Carolina
Carolina Biooncology Institute Not yet 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
Virginia Cancer Specialist Not yet recruiting
Fairfax, Virginia, United States, 22031
Principal Investigator: Alexander Spira, MD         
Sponsors and Collaborators
MacroGenics
Investigators
Study Director: Minori Rosales, MD PhD MacroGenics

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT03729596     History of Changes
Other Study ID Numbers: CP-MGC018-01
First Posted: November 2, 2018    Key Record Dates
Last Update Posted: November 2, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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
anti-PD-1

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs