Safety Study of MGD009 in B7-H3-expressing Tumors

February 4, 2022 updated by: MacroGenics

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

67

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with adverse events
Time Frame: 28 days after last dose of study drug
adverse events, serious adverse events
28 days after last dose of study drug

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak plasma concentration
Time Frame: 8 days
PK of MGD009
8 days
Number of participants that develop anti-drug antibodies
Time Frame: first dose through 28 days after last dose of study drug
Proportion of patients who develop anti-MGD0009 antibodies, immunogenicity
first dose through 28 days after last dose of study drug
Change in tumor volume
Time Frame: 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.
Weeks 6, 15, 24, 33, 42, 51, 60, 69, 78, 87, 96, 105

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MacroGenics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2015

Primary Completion (ACTUAL)

November 25, 2019

Study Completion (ACTUAL)

November 25, 2019

Study Registration Dates

First Submitted

November 20, 2015

First Submitted That Met QC Criteria

December 8, 2015

First Posted (ESTIMATE)

December 11, 2015

Study Record Updates

Last Update Posted (ACTUAL)

February 8, 2022

Last Update Submitted That Met QC Criteria

February 4, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CP-MGD009-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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