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Squamous Cell Carcinoma of Head and NeckPhase 1/2NCT03729596

MGC018 With or Without MGA012 in Advanced Solid Tumors

A Phase 1/2 study testing vobramitamab duocarmazine in people with Squamous Cell Carcinoma of Head and Neck and Triple Negative Breast Cancer, run by MacroGenics at 21 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of vobramitamab duocarmazine (MGC018) in patients with advanced solid tumors. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
vobramitamab duocarmazine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
143 participants
Where
21 sitesin 4 countries
Study dates
21 Nov 2018to 18 Mar 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

21 sites in 4 countries.

21 sites in 4 countries

United States9 sites

  • The Johns Hopkins Kimmel Cancer Center

    Baltimore, Maryland, 21231

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

  • Virginia Cancer Specialist

    Fairfax, Virginia, 22031

  • START Midwest

    Grand Rapids, Michigan, 49546

  • Carolina Biooncology Institute

    Huntersville, North Carolina, 28078

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89169

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • UCLA Department of Medicine - Hematology/Oncology

    Santa Monica, California, 90404

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

Other trials in United States

Australia4 sites

  • St Vincent's Health Network (Kinghorn Cancer Centre)

    Darlinghurst, 2010

  • Austin Health - Olivia Newton John Cancer Center

    Heidelberg, 3084

  • Calvary Mater NewCastle

    Waratah, 2298

  • The University of Queensland - Princess Alexandra Hospital (PAH)

    Woolloongabba, 4105

Other trials in Australia

Poland4 sites

  • Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie Oddział Kliniczny Onkologii

    Krakow, 31-501

  • Med-Polonia Sp. z o.o.

    Poznan, 60-693

  • Magodent Sp. z o.o. Szpital Elbląska Oddział Onkologii Klinicznej/ Chemioterapii

    Warsaw, 01-748

  • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Oddział Badań Wczesnych Faz

    Warsaw, 02-781

Other trials in Poland

Spain4 sites

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Institut Català D'Oncologia - Hospital Universitari Germans Trias I Pujol

    Barcelona

  • Hospital Universitario HM Sanchinarro

    Madrid, 20850

  • Hospital Ruber Internacional

    Madrid, 28034

Other trials in Spain

About this study

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

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of vobramitamab duocarmazine (MGC018) in patients with advanced solid tumors. 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.

Being tested
vobramitamab duocarmazine
Keywords
antibody-drug conjugate (ADC), B7-H3
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Triple Negative Breast Neoplasms, Melanoma, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • vobramitamab duocarmazineBiological

    Also called MGC018

    Anti-B7H3 antibody drug conjugate

Study groups in NCT03729596
Study groupRoleWhat they receive
Cohort 1Experimental0.5 mg/kg IV every 3 weeks
Receives: Biological: vobramitamab duocarmazine
Cohort 2Experimental1.0 mg/kg IV every 3 weeks
Receives: Biological: vobramitamab duocarmazine
Cohort 3Experimental2.0 mg/kg IV every 3 weeks
Receives: Biological: vobramitamab duocarmazine
Cohort 4Experimental3.0 mg/kg IV every 3 weeks
Receives: Biological: vobramitamab duocarmazine
Cohort 5Experimental4.0 mg/kg IV every 3 weeks
Receives: Biological: vobramitamab duocarmazine
mCRPC expansionExperimental3.0 mg/kg IV every 3 weeks
Receives: Biological: vobramitamab duocarmazine
NSCLC expansionExperimental3.0 mg/kg IV every 3 weeks
Receives: Biological: vobramitamab duocarmazine
TNBC expansionExperimental3.0 mg/kg IV every 3 weeks
Receives: Biological: vobramitamab duocarmazine
Melanoma expansionExperimental3.0 mg/kg IV every 3 weeks
Receives: Biological: vobramitamab duocarmazine
SCCHN expansionExperimental3.0 mg/kg IV every 3 weeks
Receives: Biological: vobramitamab duocarmazine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03

    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.

    Measured: Throughout the study up to 24 months

  2. Number of Participants With Dose Limiting Toxicities (DLT)

    Number of participants with severe side effects from study treatment during the DLT evaluation period (6 weels)

    Measured: up to 42 days from first dose

Secondary outcomes (14)

  1. Best Overall Response (BOR) of Vobramitamab Duocarmazine

    The best response recorded from the start of the study treatment until the end of treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1, taking into account any requirement for confirmation of response.

    Complete response (CR) is defined as disappearance of all target and non-target lesions.

    Partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, no progression of non-target lesions, and no new lesions.

    Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or unequivocal progression of non-target lesions, or appearance of new lesions.

    Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as progression.

    Not evaluable (NE) is where the response cannot be determined.

    Measured: Throughout the study for up to 24 months

  2. Objective Response Rate (ORR) of Vobramitamab Duocarmazine

    The percentage of participants who achieve a complete response (CR or partial response (PR) to treatment with vobramitamab duocarmazine

    Measured: Efficacy evaluations every 9 weeks throughout the study for up to 24 months

  3. Progression Free Survival (PFS) of Vobramitamab Duocarmazine

    PFS is calculated from the first dose date until the date of first documented PD using RECIST v1.1, or death from any cause, whichever occurs first.

    Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or unequivocal progression of non-target lesions, or appearance of new lesions. Median PFS and 95% CI is estimated using the Kaplan-Meier method.

    Measured: Every 9 weeks for up to 24 months

  4. Median Duration of Response (DoR) of Vobramitamab Duocarmazine

    Median DoR assessed as the time from the date of initial objective response to the date of first documented PD, per RECIST v1.1, or the date of death from any cause, whichever occurs first.

    Median DoR and 95% CI is estimated using the Kaplan-Meier method.

    Measured: Throughout the study for up to 48 months

  5. Median Overall Survival (OS) of Vobramitamab Duocarmazine

    Median OS assessed as the time from the first dose date to the date of death from any cause, using the Kaplan-Meier method for estimating median and confidence interval. .

    Measured: Every 9 weeks for up to 24 months

  6. PSA Response Rate

    Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA) with confirmation at least 3 weeks later

    Measured: Every 3 weeks up to 24 months

  7. Best PSA Response

    For prostate cancer patients, the greatest change from baseline in PSA.

    Measured: Every 3 weeks up to 24 months

  8. Mean Area Under the Curve (AUC) of Vobramitamab Duocarmazine Antibody Drug Conjugate (ADC)

    Area under the plasma concentration versus time curve of vobramitamab duocarmazine

    Measured: At baseline, Cycle 1, Day 1: 1 hour, 4 hours after the first dose, Day 2, Day 3, Day 7, Day 14 and Cycle 2 Day 1 (approximately 21 days after the first dose).

  9. Mean AUC of Duocarmycin

    Area under the plasma concentration versus time curve of duocarmycin (unconjugated payload) in the bloodstream

    Measured: At baseline, Cycle 1, Day 1: 1 hour, 4 hours after the first dose, Day 2, Day 3, Day 7, Day 14 and Cycle 2 Day 1 (approximately 21 days after the first dose).

  10. Mean Maximum Concentration Vobramitamab Duocarmazine ADC

    Maximum Plasma Concentration of vobramitamab duocarmazine ADC in the bloodstream

    Measured: At baseline, Cycle 1, Day 1, 1 and 4 hours after the end of infusion, Day 2, and Day 3.

  11. Mean Maximum Concentration Duocarmycin

    Maximum Plasma Concentration of vobramitamab duocarmazine ADC in the bloodstream

    Measured: At baseline, Cycle 1, Day 1, 1 and 4 hours after the end of infusion, Day 2, and Day 3.

  12. Mean Trough Concentration of Vobramitamab Duocarmazine ADC

    Average trough plasma concentration of vobramitamab duocarmazine ADC in the bloodstream.

    Measured: At baseline, and before subsequent infusion Cycle 2, Day 1 (Study Day 22).

  13. Mean Trough Concentration of Duocarmycin

    Average trough plasma concentration of duocarmycin unconjugated payload in the bloodstream.

    Measured: At baseline, and before subsequent infusion Cycle 2, Day 1 (Study Day 22).

  14. Number of Participants Who Develop MGC018 Anti-drug Antibodies

    Shifts in MGC018 anti-drug antibodies after treatment with vobramitamab duocarmazine

    Measured: Every 3 weeks through end of treatment, up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Nov 2018
  2. Study start21 Nov 2018
  3. Primary completion18 Mar 2023
  4. Study completion18 Mar 2023

Why it stopped: Business decision

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
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)
Enrolment
143 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03729596
Sponsor's protocol ID
CP-MGC018-01
Status last verified
Jul 2025
First submitted
30 Oct 2018
Last updated
31 Jul 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing vobramitamab duocarmazine in people with Squamous Cell Carcinoma of Head and Neck and Triple Negative Breast Cancer, run by MacroGenics at 21 sites in 4 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 12 inclusion and 15 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 31 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States, Australia, Poland, Spain. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03 (time frame: Throughout the study up to 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03729596.

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 31 Jul 2025.

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