MesotheliomaPhase 1NCT02628535
Safety Study of MGD009 in B7-H3-expressing Tumors
A Phase 1 study testing MGD009 in people with Mesothelioma and Bladder Cancer, run by MacroGenics at 20 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mesothelioma, Bladder Cancer, Melanoma
- What is being tested?
- MGD009
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 20 sitesin 3 countries
- Study dates
- Sep 2015to 25 Nov 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
20 sites in 3 countries.
20 sites in 3 countries
United States14 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Mary Crowley Cancer Research Center
Dallas, Texas, 75230
Virginia Cancer Specialists
Fairfax, Virginia, 22034
Carolina BioOncology Institute
Huntersville, North Carolina, 28078
UCLA
Los Angeles, California, 90095
Henry-Joyce Cancer Center
Nashville, Tennessee, 37232
New York University
New York, New York, 10016
Columbia University Medical Center
New York, New York, 10032
Stanford University School of Medicine
Palo Alto, California, 94304
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, 78229
University of California - San Francisco
San Francisco, California, 94143
Georgetown University
Washington D.C., District of Columbia, 20007
Australia5 sites
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Saint Vincent's Hospital Sydney
Darlinghurst, New South Wales, 2010
Austin Health
Heidelberg, Victoria, 3084
Linear Clinical Research
Nedlands, Western Australia, 6009
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
About this study
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
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.
Read the 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).
- Conditions
- Mesothelioma, Bladder Cancer, Melanoma, Squamous Cell Carcinoma of the Head and Neck, Non Small Cell Lung Cancer, Clear Cell Renal Cell Carcinoma
- Being tested
- MGD009
- Keywords
- B7-H3-expressing neoplasms
- Medical subject headings
- Mesothelioma, Urinary Bladder Neoplasms, Melanoma, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Ovarian Neoplasms, Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MGD009Biological
Also called orlotamab
B7-H3 x CD3 DART protein
| Study group | Role | What they receive |
|---|---|---|
| MGD009 | Experimental | Orlotamab; Humanized B7-H3 x CD3 Dual-Affinity Re-Targeting (DART®) Protein Receives: Biological: MGD009 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events
adverse events, serious adverse events
Measured: 28 days after last dose of study drug
Secondary outcomes (3)
Peak plasma concentration
PK of MGD009
Measured: 8 days
Number of participants that develop anti-drug antibodies
Proportion of patients who develop anti-MGD0009 antibodies, immunogenicity
Measured: first dose through 28 days after last dose of study drug
Change in tumor volume
Anti-tumor activity of MGD009 using both conventional RECIST 1.1 and immune-related RECIST criteria.
Measured: Weeks 6, 15, 24, 33, 42, 51, 60, 69, 78, 87, 96, 105
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2015 (estimated)
- Study startSep 2015
- Primary completion25 Nov 2019
- Study completion25 Nov 2019
Why it stopped: Business decision (not for safety reasons)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MesotheliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- MacroGenics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02628535
- Sponsor's protocol ID
- CP-MGD009-01
- Status last verified
- Feb 2022
- First submitted
- 20 Nov 2015
- Last updated
- 8 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02628535
- Acronym / sponsor ID
- CP-MGD009-01
- Conditions
- Mesothelioma, Bladder Cancer, Melanoma, Squamous Cell Carcinoma of the Head and Neck, Non Small Cell Lung Cancer, Clear Cell Renal Cell Carcinoma
- Keywords
- B7-H3-expressing neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business decision (not for safety reasons)
- Enrolment
- 67 participants (actual)
- Lead sponsor
- MacroGenicsIndustry (pharma, biotech, devices)
- Study start
- Sep 2015
- Primary completion
- 25 Nov 2019 (actual)
- Study completion
- 25 Nov 2019 (actual)
- First posted
- 11 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MGD009 | Experimental | Biological: MGD009Orlotamab; Humanized B7-H3 x CD3 Dual-Affinity Re-Targeting (DART®) Protein |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MGD009Also: orlotamabB7-H3 x CD3 DART protein | Biological | MGD009 |
Primary outcome
Number of participants with adverse events
Time frame: 28 days after last dose of study drug
adverse events, serious adverse events
3 secondary outcomes
Peak plasma concentration
Time frame: 8 days
Number of participants that develop anti-drug antibodies
Time frame: 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
Results and safety
The study was stopped early (reason given: Business decision (not for safety reasons)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
20 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MGD009 in people with Mesothelioma and Bladder Cancer, run by MacroGenics at 20 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business decision (not for safety reasons)). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (time frame: 28 days after last dose of study drug). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2022.