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

NCT ID: NCT02475213

Last Updated: 2025-08-11

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

146 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-31

Study Completion Date

2021-08-18

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Melanoma Head and Neck Cancer Non Small Cell Lung Cancer Urothelial Carcinoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Cohort 1

Enoblituzumab 3 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks

Group Type EXPERIMENTAL

Enoblituzumab Schedule 1

Intervention Type BIOLOGICAL

enoblituzumab is administered by IV infusion once per week for up to 51 doses.

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.

Cohort 2

Enoblituzumab 10 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks

Group Type EXPERIMENTAL

Enoblituzumab Schedule 1

Intervention Type BIOLOGICAL

enoblituzumab is administered by IV infusion once per week for up to 51 doses.

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.

Cohort 3

Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks

Group Type EXPERIMENTAL

Enoblituzumab Schedule 1

Intervention Type BIOLOGICAL

enoblituzumab is administered by IV infusion once per week for up to 51 doses.

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.

Cohort 4

Enoblituzumab 15 mg/kg IV plus retifanlimab 375 mg IV every 3 weeks

Group Type EXPERIMENTAL

Enoblituzumab Schedule 2

Intervention Type BIOLOGICAL

Enoblituzumab is administered by IV infusion every 3 weeks for up to 17 doses

retifanlimab

Intervention Type BIOLOGICAL

Retifanlimab is administered by IV infusion every 3 weeks for up to 17 doses

Melanoma Cohort

Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks

Group Type EXPERIMENTAL

Enoblituzumab Schedule 1

Intervention Type BIOLOGICAL

enoblituzumab is administered by IV infusion once per week for up to 51 doses.

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.

Urothelial Cancer Cohort

Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks

Group Type EXPERIMENTAL

Enoblituzumab Schedule 1

Intervention Type BIOLOGICAL

enoblituzumab is administered by IV infusion once per week for up to 51 doses.

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.

Non-small Cell Cancer (NSCLC) Cohort

Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks

Group Type EXPERIMENTAL

Enoblituzumab Schedule 1

Intervention Type BIOLOGICAL

enoblituzumab is administered by IV infusion once per week for up to 51 doses.

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.

Squamous Cell Cancer of Head and Neck (SCCHN) Cohort

Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks

Group Type EXPERIMENTAL

Enoblituzumab Schedule 1

Intervention Type BIOLOGICAL

enoblituzumab is administered by IV infusion once per week for up to 51 doses.

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Enoblituzumab Schedule 1

enoblituzumab is administered by IV infusion once per week for up to 51 doses.

Intervention Type BIOLOGICAL

Pembrolizumab

Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.

Intervention Type BIOLOGICAL

Enoblituzumab Schedule 2

Enoblituzumab is administered by IV infusion every 3 weeks for up to 17 doses

Intervention Type BIOLOGICAL

retifanlimab

Retifanlimab is administered by IV infusion every 3 weeks for up to 17 doses

Intervention Type BIOLOGICAL

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

MGA271 Keytruda MGA271 INCMGA00012 MGA012

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

MacroGenics

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Ashley Ward, MD

Role: STUDY_DIRECTOR

MacroGenics

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Mayo Clinic - AZ

Scottsdale, Arizona, United States

Site Status

Christiana Care Health Services, Inc.

Newark, Delaware, United States

Site Status

Mayo Clinic - FL

Jacksonville, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Norton Cancer Institute Research Program

Louisville, Kentucky, United States

Site Status

University of Maryland Greenbaum Cancer Center

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

South Texas Accelerated Research Therapeutics, LLC - Midwest

Grand Rapids, Michigan, United States

Site Status

Mayo Clinic - MN

Rochester, Minnesota, United States

Site Status

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Gabrail Cancer Institute

Canton, Ohio, United States

Site Status

Hospital of the University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburg

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Greenville Health System

Greenville, South Carolina, United States

Site Status

Mary Crowley Cancer Research Center

Dallas, Texas, United States

Site Status

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 35414591 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CP-MGA271-03

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Pembrolizumab in Neoplasms or Lymphomas
NCT03316573 SUSPENDED PHASE2