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Safety Study of MGD009 in B7-H3-expressing Tumors

Sponsor
MacroGenics (Industry)
Overall Status
Terminated
CT.gov ID
NCT02628535
Collaborator
(none)
67
Enrollment
20
Locations
1
Arm
50.8
Duration (Months)
3.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety of MGD009 when given to patients with B7-H3-expressing tumors. The study will also evaluate what is the highest dose of MGD009 that can be given safely. Assessments will be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics (PD) and to evaluate potential anti-tumor activity of MGD009.

Condition or Disease Intervention/Treatment Phase
  • Biological: MGD009
 Phase 1

Detailed Description

This study is a Phase 1 open-label, dose escalation, cohort expansion, and efficacy follow-up study of MGD009 administered intravenously (IV) on an every-other-week schedule for up to one year (14 cycles).

The dose escalation phase is designed to characterize the safety and tolerability of MGD009 and to define the maximum tolerated or maximum administered dose (MTD/MAD). This phase will enroll patients with mesothelioma, bladder cancer, melanoma, squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (ccRCC), ovarian cancer, thyroid cancer, triple-negative breast cancer (TNBC), pancreatic cancer, colon cancer, soft tissue sarcoma, or prostate cancer.

In the cohort expansion phase, 6 cohorts of 16 patients each will be enrolled to further evaluate the safety and potential efficacy of MGD009 administered at the MTD/MAD dose in patients with mesothelioma, bladder cancer, melanoma, SCCHN, NSCLC, or other specific tumors that express high levels of B7-H3. Pre- and on-study biopsies are required for melanoma patients in the cohort expansion phase. Two additional cohorts (up to15 patients each) will evaluate the use of prophylaxis therapies to mitigate toxicity.

The survival follow-up phase consists of the 2-year period after the final dose of study drug.

All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid Tumors (RECIST) and immune-related response criteria (irRC).

Study Design

Study Type:
Interventional
Actual Enrollment :
67 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1, First-in-Human, Open Label, Dose Escalation Study of MGD009, A Humanized B7-H3 x CD3 Dual-Affinity Re-Targeting (DART) Protein in Patients With Unresectable or Metastatic B7-H3-Expressing Neoplasms
Study Start Date :
Sep 1, 2015
Actual Primary Completion Date :
Nov 25, 2019
Actual Study Completion Date :
Nov 25, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: MGD009

Orlotamab; Humanized B7-H3 x CD3 Dual-Affinity Re-Targeting (DART®) Protein

Biological: MGD009
B7-H3 x CD3 DART protein
Other Names:
  • orlotamab

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of participants with adverse events [28 days after last dose of study drug]

      adverse events, serious adverse events

    Secondary Outcome Measures

    1. Peak plasma concentration [8 days]

      PK of MGD009

    2. Number of participants that develop anti-drug antibodies [first dose through 28 days after last dose of study drug]

      Proportion of patients who develop anti-MGD0009 antibodies, immunogenicity

    3. Change in tumor volume [Weeks 6, 15, 24, 33, 42, 51, 60, 69, 78, 87, 96, 105]

      Anti-tumor activity of MGD009 using both conventional RECIST 1.1 and immune-related RECIST criteria.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Histologically and/or cytologically proven unresectable locally advanced or metastatic tumors that express B7-H3 on the membrane or vasculature. The requirement for previous systemic therapy may be waived if a person was intolerant of standard front-line therapy

    • Dose escalation phase prior systemic treatment requirements:

    • pleural mesothelioma, pancreatic cancer: 1-3 prior treatments

    • urothelial, SCHNN, prostate, soft tissue sarcoma, prostate cancer, TNBC, ccRCC, NSCLC: 1-5 prior treatments

    • ovarian cancer: 2-4 prior treatments

    • colon cancer: 2-4 prior treatments

    • cutaneous melanoma: at least 1 prior treatment (including immunotherapy).

    • Patients with prior immune checkpoint inhibitors must have related toxicities reduced to Grade 0, 1, or baseline

    • Measurable disease per RECIST 1.1 criteria

    • Easter Cooperative Oncology Group (ECOG) performance status 0 or 1

    • Acceptable laboratory parameters and adequate organ reserve.

    Exclusion Criteria:

    • Patients with central nervous system (CNS) involvement must have been treated, be asymptomatic, do not exhibit progression of CNS metastases on MRI or CT within 28 days, and do not have concurrent leptomeningeal disease or cord compression.

    • Clinically significant pulmonary compromise within 28 days of first dose, including pneumonia, pneumonitis, requirement for supplemental oxygen). use to maintain adequate oxygenation, or pleural effusion sufficient to warrant pleurocentesis or any history of ≥ Grade 3 drug induced or radiation pneumonitis.

    • 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 Hashimoto's or Grave's disease that are now euthyroid clinically and by lab testing

    • History of clinically-significant cardiovascular disease, or cardiac arrhythmias, including atrial fibrillation at screening or day of treatment

    • History of clinically-significant gastrointestinal (GI) disease; GI perforation within 1 year; GI bleeding or acute pancreatitis within 3 months; or diverticulitis within 4 weeks of first study drug administration

    • 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 (PCR)

    • 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

    • Treatment with systemic cancer therapy or investigational therapy within 3 weeks of first study drug administration; 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

    • Trauma or major surgery within 4 weeks of first study drug administration

    • Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient contained in the drug or vehicle formulation for MGD009

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCLA Los Angeles California United States 90095
    2 Stanford University School of Medicine Palo Alto California United States 94304
    3 University of California - San Francisco San Francisco California United States 94143
    4 Georgetown University Washington District of Columbia United States 20007
    5 Massachusetts General Hospital Boston Massachusetts United States 02114
    6 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    7 New York University New York New York United States 10016
    8 Columbia University Medical Center New York New York United States 10032
    9 Carolina BioOncology Institute Huntersville North Carolina United States 28078
    10 Penn Presbyterian Medical Center Philadelphia Pennsylvania United States 19104
    11 Henry-Joyce Cancer Center Nashville Tennessee United States 37232
    12 Mary Crowley Cancer Research Center Dallas Texas United States 75230
    13 South Texas Accelerated Research Therapeutics, LLC San Antonio Texas United States 78229
    14 Virginia Cancer Specialists Fairfax Virginia United States 22034
    15 Chris O'Brien Lifehouse Camperdown New South Wales Australia 2050
    16 Saint Vincent's Hospital Sydney Darlinghurst New South Wales Australia 2010
    17 Princess Alexandra Hospital Woolloongabba Queensland Australia 4102
    18 Austin Health Heidelberg Victoria Australia 3084
    19 Linear Clinical Research Nedlands Western Australia Australia 6009
    20 Princess Margaret Cancer Centre Toronto Ontario Canada M5G1Z5

    Sponsors and Collaborators

    • MacroGenics

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    MacroGenics
    ClinicalTrials.gov Identifier:
    NCT02628535
    Other Study ID Numbers:
    • CP-MGD009-01
    First Posted:
    Dec 11, 2015
    Last Update Posted:
    Feb 8, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by MacroGenics
    B7-H3-expressing neoplasms
    Additional relevant MeSH terms:
    Carcinoma
    Sarcoma
    Carcinoma, Renal Cell
    Mesothelioma
    Squamous Cell Carcinoma of Head and Neck

    Study Results

    No Results Posted as of Feb 8, 2022