Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab or MGA012 in Refractory Cancer

August 4, 2025 updated by: MacroGenics

A Phase 1, Open-Label, Dose Escalation Study of MGA271 in Combination With Pembrolizumab and in Combination With MGA012 in Patients With Melanoma, Squamous Cell Cancer of the Head and Neck, Non-Small Cell Lung Cancer, Urothelial Cancer, and Other Cancers

The purpose of this study is to evaluate the safety of enoblituzumab (MGA271) in combination with Keytruda (pembrolizumab) when given to patients with B7-H3-expressing melanoma, squamous cell carcinoma of the head and neck (SCCHN), non small cell lung cancer (NSCLC), Urothelial Cancer and other B7-H3 expressing cancers. The study will also evaluate what is the highest dose of enoblituzumab that can be given safely when given with pembrolizumab. Assessments will also be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics) and to evaluate potential anti-tumor activity of MGA271 in combination with pembrolizumab. Safety and efficacy of enoblituzumab in combination with MGA012 (anti-PD-1 monoclonal antibody; also known as INCMGA00012) will also be evaluated.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
146

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic - AZ
    • Delaware
      • Newark, Delaware, United States, 19713
        • Christiana Care Health Services, Inc.
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic - FL
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute Research Program
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Greenbaum Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • South Texas Accelerated Research Therapeutics, LLC - Midwest
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic - MN
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Nebraska Cancer Specialists
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania/Abramson Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburg
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Greenville Health System
    • Texas
      • Dallas, Texas, United States, 75230
        • Mary Crowley Cancer Research Center
      • San Antonio, Texas, United States, 78229
        • South Texas Accelerated Research Therapeutics, LLC

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • To enroll on cohorts 1-4, participants must have a histologically-proven, previously treated, unresectable, locally advanced or metastatic mesothelioma, urothelial cancer, thyroid cancer, pancreatic cancer, ovarian cancer, colon cancer, prostate cancer, soft tissue sarcoma, triple negative breast cancer, renal clear cell cancer, melanoma, squamous cell cancer of the head and neck, or non-small cell lung cancer.
  • Participants on the melanoma cohort must have progressed on or after at least one anti-PD-L1 or anti- PD-1 containing therapy.
  • Participants on the SCCHN cohort must have progressed on or after platinum-based systemic therapy
  • Participants on the NSCLC cohort must have progressed on or after first line systemic therapy
  • Participants on the urothelial cancer cohort must have received at least one platinum-containing regimen and have progressed on or after an anti-PD-L1 or anti-PD-1 containing therapy
  • 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 a history of symptomatic central nervous system metastases, unless treated and asymptomatic
  • Patients with 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 Grave's disease that are now euthyroid clinically and by lab testing
  • History of allogeneic bone marrow, stem cell, or solid organ transplant
  • Treatment with systemic cancer therapy or investigational therapy within 4 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
  • History of clinically-significant cardiovascular disease; gastrointestinal perforation; gastrointestinal bleeding, acute pancreatitis 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
  • Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient contained in the drug or vehicle formulation for MGA271 or pembrolizumab.

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: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1
Enoblituzumab 3 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Biological: Pembrolizumab
Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.
Other Names:
  • Keytruda
Biological: Enoblituzumab Schedule 1
enoblituzumab is administered by IV infusion once per week for up to 51 doses.
Other Names:
  • MGA271
Experimental: Cohort 2
Enoblituzumab 10 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Biological: Pembrolizumab
Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.
Other Names:
  • Keytruda
Biological: Enoblituzumab Schedule 1
enoblituzumab is administered by IV infusion once per week for up to 51 doses.
Other Names:
  • MGA271
Experimental: Cohort 3
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Biological: Pembrolizumab
Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.
Other Names:
  • Keytruda
Biological: Enoblituzumab Schedule 1
enoblituzumab is administered by IV infusion once per week for up to 51 doses.
Other Names:
  • MGA271
Experimental: Cohort 4
Enoblituzumab 15 mg/kg IV plus retifanlimab 375 mg IV every 3 weeks
Biological: Enoblituzumab Schedule 2
Enoblituzumab is administered by IV infusion every 3 weeks for up to 17 doses
Other Names:
  • MGA271
Biological: retifanlimab
Retifanlimab is administered by IV infusion every 3 weeks for up to 17 doses
Other Names:
  • INCMGA00012
  • MGA012
Experimental: Melanoma Cohort
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Biological: Pembrolizumab
Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.
Other Names:
  • Keytruda
Biological: Enoblituzumab Schedule 1
enoblituzumab is administered by IV infusion once per week for up to 51 doses.
Other Names:
  • MGA271
Experimental: Urothelial Cancer Cohort
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Biological: Pembrolizumab
Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.
Other Names:
  • Keytruda
Biological: Enoblituzumab Schedule 1
enoblituzumab is administered by IV infusion once per week for up to 51 doses.
Other Names:
  • MGA271
Experimental: Non-small Cell Cancer (NSCLC) Cohort
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Biological: Pembrolizumab
Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.
Other Names:
  • Keytruda
Biological: Enoblituzumab Schedule 1
enoblituzumab is administered by IV infusion once per week for up to 51 doses.
Other Names:
  • MGA271
Experimental: Squamous Cell Cancer of Head and Neck (SCCHN) Cohort
Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Biological: Pembrolizumab
Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.
Other Names:
  • Keytruda
Biological: Enoblituzumab Schedule 1
enoblituzumab is administered by IV infusion once per week for up to 51 doses.
Other Names:
  • MGA271

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Dose-limiting Toxicities (DLT) After Administration of Enoblituzumab and Pembrolizumab or Retifanlimab
Time Frame: Study Day 1-42, for Cohorts 1-4.
Dose-limiting toxicities are severe side effects related to study treatment that may cause dose interruptions, dose reductions, or withdrawal of treatment.
Study Day 1-42, for Cohorts 1-4.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Maximum Concentration of Enoblituzumab
Time Frame: Baseline, 1, 4, 24, and 72 hours after the first dose.
The highest measured concentration of enoblizuzumab in the bloodstream.
Baseline, 1, 4, 24, and 72 hours after the first dose.
Mean Trough Concentration of Enoblituzumab
Time Frame: At baseline, and Day 7.

Trough concentration is the concentration measured before the a subsequent dose of enoblituzumab.

MGA271 is characterized by a biphasic concentration-time profile and PPK was used to estimate PK parameters at each dose level
At baseline, and Day 7.
Mean Area Under the Concentration Time Curve (AUC) From Time 0 to Day 7 of Enoblituzumab
Time Frame: At baseline, 1, 4, 24, 72 hours, and Day 7.
AUC is the total body exposure to enoblituzumab MGA271 is characterized by a biphasic concentration-time profile and PPK was used to estimate PK parameters at each dose level
At baseline, 1, 4, 24, 72 hours, and Day 7.
Mean Clearance of Enoblituzumab
Time Frame: At baseline, 1, 4, 24, 72 hours, and Day 7.
Drug clearance is the amount of drug removed from the bloodstream by the body per unit of time.
At baseline, 1, 4, 24, 72 hours, and Day 7.
Mean Volume of Distribution at Steady State of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab
Time Frame: At baseline, 1, 4, 24, and 72 and Day 7.
The volume of distribution is related to how much drug is distributed to body tissues, or remains in the bloodstream
At baseline, 1, 4, 24, and 72 and Day 7.
Mean Terminal Half-life of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab
Time Frame: At baseline, 1, 4, 24, and 72 and Day 7.
Terminal half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium MGA271 is characterized by a biphasic concentration-time profile and PPK was used to estimate PK parameters at each dose level
At baseline, 1, 4, 24, and 72 and Day 7.
Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA)
Time Frame: Every 3 weeks throughout the study, average duration 13 months.
Every 3 weeks throughout the study, average duration 13 months.
Number of Participants That Develop Retifanlimab ADA
Time Frame: Every 3 weeks throughout the study, average duration 13 months.
Every 3 weeks throughout the study, average duration 13 months.
Objective Response Rate
Time Frame: Six weeks after the first dose, then every 9 weeks throughout study until discontinuation, average 13 months
The number of participants with a complete response (CR) or partial response (PR) to enoblituzumab in combination with pembrolizumab or retifanlimab RECIST 1.1 criteria.
Six weeks after the first dose, then every 9 weeks throughout study until discontinuation, average 13 months
ORR Using Immune-related (ir) RECIST Criteria
Time Frame: Six weeks after the first dose, then every 9 weeks throughout study until discontinuation, average 13 months
The number of participants with a complete response (CR) or partial response (PR) to enoblituzumab in combination with pembrolizumab or retifanlimab using irRECIST 1.1 criteria.
Six weeks after the first dose, then every 9 weeks throughout study until discontinuation, average 13 months
Best Overall Response (RECIST 1.1)
Time Frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
The participants best response to treatment during their study participation. Responses are categorized as CR, PR, stable disease (SD), progressive disease (PD) or not evaluated (NE)
Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
Best Overall Response (irRECIST 1.1)
Time Frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
The participants best response to treatment during their study participation. Responses are categorized as CR, PR, stable disease (SD), progressive disease (PD) or not evaluated (NE)
Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1
Time Frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average13 months.
The duration of response displays the minimum and maximum range in months from the first documented CR or PR until disease progression or death, whichever is first.
Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average13 months.
Minimum and Maximum DoR Per RECIST 1.1
Time Frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
The duration of response displays the minimum and maximum range in months from the first documented CR or PR until disease progression or death, whichever is first.
Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
Median Progression-free Survival (PFS) Using RECIST 1.1
Time Frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
The time from the first infusion of pembrolizumab or retifanlimab until documented disease progression or death from any cause.
Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
Median PFS Using irRECIST 1.1 Criteria
Time Frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
The time from the first infusion of pembrolizumab or retifanlimab until documented disease progression or death from any cause.
Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
Median Overall Survival
Time Frame: Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.
The time from the first infusion of pembrolizumab or retifanlimab until death from any cause.
Evaluated at 6 weeks then every 9 weeks throughout the study until discontinuation, average 13 months.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
MacroGenics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Ashley Ward, MD, MacroGenics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 18, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 18, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 16, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 16, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 18, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 11, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 4, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CP-MGA271-03

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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