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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. Identifier: NCT03729596
Recruitment Status : Recruiting
First Posted : November 2, 2018
Last Update Posted : October 22, 2021
Information provided by (Responsible Party):

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
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 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), 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.

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 : 182 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. Best PSA response [ Time Frame: 24 months ]
    The greatest change from baseline in PSA.

  4. 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

  5. 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

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

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

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

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

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

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

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

  13. 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

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.
  • 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.

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, 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

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 identifier (NCT number): NCT03729596

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Contact: Joanna Lohr, PhD (240) 552-8030

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Sponsors and Collaborators
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Study Director: Chet Bohac, PharmD MD MSc MacroGenics
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Responsible Party: MacroGenics Identifier: NCT03729596    
Other Study ID Numbers: CP-MGC018-01
First Posted: November 2, 2018    Key Record Dates
Last Update Posted: October 22, 2021
Last Verified: October 2021
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)
Additional relevant MeSH terms:
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Triple Negative Breast Neoplasms
Squamous Cell Carcinoma of Head and Neck
Neoplasms by Site
Neoplasms by Histologic Type
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Breast Neoplasms
Breast Diseases
Skin Diseases
Head and Neck Neoplasms