Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab or MGA012 in Refractory Cancer
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
1 other identifier
interventional
146
1 country
20
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2015
Longer than P75 for phase_1
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 16, 2015
CompletedFirst Posted
Study publicly available on registry
June 18, 2015
CompletedStudy Start
First participant enrolled
July 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 18, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
August 18, 2021
CompletedResults Posted
Study results publicly available
August 11, 2025
CompletedAugust 11, 2025
August 1, 2025
6.1 years
June 16, 2015
February 14, 2023
August 4, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants With Dose-limiting Toxicities (DLT) After Administration of Enoblituzumab and Pembrolizumab or Retifanlimab
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 Outcomes (17)
Mean Maximum Concentration of Enoblituzumab
Baseline, 1, 4, 24, and 72 hours after the first dose.
Mean Trough Concentration of Enoblituzumab
At baseline, and Day 7.
Mean Area Under the Concentration Time Curve (AUC) From Time 0 to Day 7 of Enoblituzumab
At baseline, 1, 4, 24, 72 hours, and Day 7.
Mean Clearance of Enoblituzumab
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
At baseline, 1, 4, 24, and 72 and Day 7.
- +12 more secondary outcomes
Study Arms (8)
Cohort 1
EXPERIMENTALEnoblituzumab 3 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Cohort 2
EXPERIMENTALEnoblituzumab 10 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Cohort 3
EXPERIMENTALEnoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Cohort 4
EXPERIMENTALEnoblituzumab 15 mg/kg IV plus retifanlimab 375 mg IV every 3 weeks
Melanoma Cohort
EXPERIMENTALEnoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Urothelial Cancer Cohort
EXPERIMENTALEnoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Non-small Cell Cancer (NSCLC) Cohort
EXPERIMENTALEnoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Squamous Cell Cancer of Head and Neck (SCCHN) Cohort
EXPERIMENTALEnoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Interventions
enoblituzumab is administered by IV infusion once per week for up to 51 doses.
Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.
Enoblituzumab is administered by IV infusion every 3 weeks for up to 17 doses
Retifanlimab is administered by IV infusion every 3 weeks for up to 17 doses
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MacroGenicslead
Study Sites (20)
Mayo Clinic - AZ
Scottsdale, Arizona, 85259, United States
Christiana Care Health Services, Inc.
Newark, Delaware, 19713, United States
Mayo Clinic - FL
Jacksonville, Florida, 32224, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Norton Cancer Institute Research Program
Louisville, Kentucky, 40202, United States
University of Maryland Greenbaum Cancer Center
Baltimore, Maryland, 21201, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
South Texas Accelerated Research Therapeutics, LLC - Midwest
Grand Rapids, Michigan, 49503, United States
Mayo Clinic - MN
Rochester, Minnesota, 55905, United States
Nebraska Cancer Specialists
Omaha, Nebraska, 68130, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Columbia University Medical Center
New York, New York, 10032, United States
Gabrail Cancer Institute
Canton, Ohio, 44718, United States
Hospital of the University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburg
Pittsburgh, Pennsylvania, 15232, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Greenville Health System
Greenville, South Carolina, 29605, United States
Mary Crowley Cancer Research Center
Dallas, Texas, 75230, United States
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, 78229, United States
Related Publications (1)
Aggarwal C, Prawira A, Antonia S, Rahma O, Tolcher A, Cohen RB, Lou Y, Hauke R, Vogelzang N, P Zandberg D, Kalebasty AR, Atkinson V, Adjei AA, Seetharam M, Birnbaum A, Weickhardt A, Ganju V, Joshua AM, Cavallo R, Peng L, Zhang X, Kaul S, Baughman J, Bonvini E, Moore PA, Goldberg SM, Arnaldez FI, Ferris RL, Lakhani NJ. Dual checkpoint targeting of B7-H3 and PD-1 with enoblituzumab and pembrolizumab in advanced solid tumors: interim results from a multicenter phase I/II trial. J Immunother Cancer. 2022 Apr;10(4):e004424. doi: 10.1136/jitc-2021-004424.
PMID: 35414591DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- MacroGenics, Inc.
Study Officials
- STUDY DIRECTOR
Ashley Ward, MD
MacroGenics
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 16, 2015
First Posted
June 18, 2015
Study Start
July 1, 2015
Primary Completion
August 18, 2021
Study Completion
August 18, 2021
Last Updated
August 11, 2025
Results First Posted
August 11, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will not share