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

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: Completed
• Conditions: Melanoma; Head and Neck Cancer; Non Small Cell Lung Cancer; Urothelial Carcinoma
• Intervention / Treatment: Biological: Pembrolizumab; Biological: Enoblituzumab Schedule 1; Biological: Enoblituzumab Schedule 2; Biological: retifanlimab

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 1

Contacts and Locations

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

Eligibility Criteria

• 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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Maximum Concentration of Enoblituzumab	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	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	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	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	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	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)		Every 3 weeks throughout the study, average duration 13 months.
Number of Participants That Develop Retifanlimab ADA		Every 3 weeks throughout the study, average duration 13 months.
Objective Response Rate	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	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)	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)	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	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	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	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	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	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

• Sponsor: MacroGenics
• Investigators: Study Director: Ashley Ward, MD, MacroGenics

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): August 18, 2021
• Study Completion (Actual): August 18, 2021

Study Registration Dates

• First Submitted: June 16, 2015
• First Submitted That Met QC Criteria: June 16, 2015
• First Posted (Estimated): June 18, 2015

Study Record Updates

• Last Update Posted (Actual): August 11, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID 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