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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 2, 2021
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 2, 2021
Actual Study Start Date  ICMJE November 21, 2018
Estimated Primary Completion Date March 2022   (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: August 27, 2020)
  • 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)
  • PSA response rate [ Time Frame: 24 months ]
    Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA)
  • 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
  • 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
  • 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
  • Immunogenicity [ Time Frame: 24 months ]
    Percent of patients with anti-drug antibodies against MGC018 and MGA012
Original 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)
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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Advanced Solid Tumor, Adult
  • Metastatic Castrate Resistant Prostate Cancer
  • Non Small Cell Lung Cancer
  • Triple Negative Breast Cancer
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: August 27, 2020)
150
Original Estimated Enrollment  ICMJE
 (submitted: October 31, 2018)
193
Estimated Study Completion Date  ICMJE May 2025
Estimated Primary Completion Date March 2022   (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 ≤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
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 Australia,   Poland,   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: No
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 February 2021

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