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MGC018 With or Without MGA012 in Advanced Solid Tumors

Sponsor
MacroGenics (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03729596
Collaborator
(none)
182
Enrollment
20
Locations
2
Arms
53.3
Anticipated Duration (Months)
9.1
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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
  • Biological: MGC018
  • Biological: retifanlimab
 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 retifanlimab, Dose Escalation and Cohort Expansion will commence only upon sponsor notification to all study investigators.

Study Design

Study Type:
Interventional
Anticipated 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.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 :
Nov 21, 2018
Anticipated Primary Completion Date :
Mar 1, 2023
Anticipated Study Completion Date :
May 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: MGC018 Monotherapy

MGC018: Anti-B7-H3 antibody drug conjugate

Biological: MGC018
Anti-B7-H3 antibody drug conjugate
Experimental: MGC018 plus retifanlimab

MGC018: Anti-B7-H3 antibody drug conjugate; retifanlimab: Anti-PD-1 antibody

Biological: MGC018
Anti-B7-H3 antibody drug conjugate

Biological: retifanlimab
Anti-PD-1 antibody
Other Names:
  • INCMGA00012
  • MGA012

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of Adverse Events of MGC018 and MGC018 + retifanlimab as assessed by CTCAE v4.03 [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 [up to 42 days from first dose]

      Maximum tolerated or maximum administered dose of MGC018 and MGC018 + retifanlimab

    Secondary Outcome Measures

    1. Preliminary anti-tumor activity of MGC018 and MGC018+retifanlimab [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 [24 months]

      Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA)

    3. Best PSA response [24 months]

      The greatest change from baseline in PSA.

    4. Radiographic progression-free survival [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 [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 [24 months]

      Area under the plasma concentration versus time curve of MGC018 and MGC018+retifanlimab

    7. Cmax [24 months]

      Maximum Plasma Concentration of MGC018 and MGC018+retifanlimab

    8. Tmax [24 months]

      Time to reach maximum (peak) plasma concentration of MGC018 and MGC018+retifanlimab

    9. Ctrough [24 months]

      Trough plasma concentration of MGC018 and MGC018+retifanlimab

    10. CL [24 months]

      Total body clearance of the drug from plasma of MGC018 and MGC018+retifanlimab

    11. Vss [24 months]

      Apparent volume of distribution at steady state of MGC018 and MGC018+retifanlimab

    12. t1/2 [24 months]

      Terminal half life of MGC018 and MGC018+retifanlimab

    13. Immunogenicity [24 months]

      Percent of patients with anti-drug antibodies against MGC018 and retifanlimab

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCLA Department of Medicine - Hematology/Oncology Santa Monica California United States 90404
    2 Sibley Memorial Hospital Washington District of Columbia United States 20016
    3 The Johns Hopkins Kimmel Cancer Center Baltimore Maryland United States 21231
    4 START Midwest Grand Rapids Michigan United States 49546
    5 Nebraska Methodist Hospital Omaha Nebraska United States 68114
    6 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89169
    7 Carolina Biooncology Institute Huntersville North Carolina United States 28078
    8 Inova Schar Cancer Institute Fairfax Virginia United States 22031
    9 Virginia Cancer Specialist Fairfax Virginia United States 22031
    10 St Vincent's Health Network (Kinghorn Cancer Centre) Darlinghurst Australia 2010
    11 Austin Health - Olivia Newton John Cancer Center Heidelberg Australia 3084
    12 Calvary Mater NewCastle Waratah Australia 2298
    13 The University of Queensland - Princess Alexandra Hospital (PAH) Woolloongabba Australia 4105
    14 Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie Oddział Kliniczny Onkologii Krakow Poland 31-501
    15 Med-Polonia Sp. z o.o. Poznań Poland 60-693
    16 Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Oddział Badań Wczesnych Faz Warsaw Poland 02-781
    17 Magodent Sp. z o.o. Szpital Elbląska Oddział Onkologii Klinicznej/ Chemioterapii Warszawa Poland 01-748
    18 Hospital Universitario Vall d'Hebron Barcelona Spain 08035
    19 Hospital Universitario HM Sanchinarro Madrid Spain 20850
    20 Hospital Ruber Internacional Madrid Spain 28034

    Sponsors and Collaborators

    • MacroGenics

    Investigators

    • Study Director: Chet Bohac, PharmD MD MSc, MacroGenics

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    MacroGenics
    ClinicalTrials.gov Identifier:
    NCT03729596
    Other Study ID Numbers:
    • CP-MGC018-01
    First Posted:
    Nov 2, 2018
    Last Update Posted:
    Mar 2, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Additional relevant MeSH terms:
    Triple Negative Breast Neoplasms
    Squamous Cell Carcinoma of Head and Neck

    Study Results

    No Results Posted as of Mar 2, 2022