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

Phase 1

Completed

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

• Registration Number: NCT02475213
• Lead Sponsor: MacroGenics

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-06-16
• Study First Submitted QC: 2015-06-16
• Study First Posted: 2015-06-18
• Study Start: 2015-07-01
• Primary Completion: 2021-08-18
• Study Completion: 2021-08-18
• Results First Submitted: 2023-02-14
• Status Verified: 2025-08
• Results First Submitted QC: 2025-08-04
• Last Update Submitted: 2025-08-04
• Results First Posted: 2025-08-11
• Last Update Posted: 2025-08-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 146

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1	Enoblituzumab Schedule 1	Enoblituzumab 3 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Cohort 1	Pembrolizumab	Enoblituzumab 3 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Melanoma Cohort	Pembrolizumab	Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Cohort 2	Enoblituzumab Schedule 1	Enoblituzumab 10 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Cohort 2	Pembrolizumab	Enoblituzumab 10 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Cohort 3	Enoblituzumab Schedule 1	Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Cohort 3	Pembrolizumab	Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Cohort 4	Enoblituzumab Schedule 2	Enoblituzumab 15 mg/kg IV plus retifanlimab 375 mg IV every 3 weeks
Cohort 4	retifanlimab	Enoblituzumab 15 mg/kg IV plus retifanlimab 375 mg IV every 3 weeks
Melanoma Cohort	Enoblituzumab Schedule 1	Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Urothelial Cancer Cohort	Enoblituzumab Schedule 1	Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Urothelial Cancer Cohort	Pembrolizumab	Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Non-small Cell Cancer (NSCLC) Cohort	Enoblituzumab Schedule 1	Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Non-small Cell Cancer (NSCLC) Cohort	Pembrolizumab	Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Squamous Cell Cancer of Head and Neck (SCCHN) Cohort	Enoblituzumab Schedule 1	Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
Squamous Cell Cancer of Head and Neck (SCCHN) Cohort	Pembrolizumab	Enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose-limiting Toxicities (DLT) After Administration of Enoblituzumab and Pembrolizumab or Retifanlimab	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.

Secondary Outcome Measures

Name	Time	Method
ORR Using Immune-related (ir) RECIST Criteria	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.
Minimum and Maximum Duration of Response (DoR) Per irRECIST 1.1	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.
Mean Maximum Concentration of Enoblituzumab	Baseline, 1, 4, 24, and 72 hours after the first dose.	The highest measured concentration of enoblizuzumab in the bloodstream.
Mean Trough Concentration of Enoblituzumab	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
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.	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
Mean Clearance of Enoblituzumab	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.
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.	The volume of distribution is related to how much drug is distributed to body tissues, or remains in the bloodstream
Best Overall Response (RECIST 1.1)	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)
Median Progression-free Survival (PFS) Using RECIST 1.1	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.
Mean Terminal Half-life of Enoblituzumab in Combination With Pembrolizumab or Retifanlimab	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
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.
Minimum and Maximum DoR Per RECIST 1.1	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.
Median PFS Using irRECIST 1.1 Criteria	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.
Objective Response Rate	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.
Best Overall Response (irRECIST 1.1)	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)
Median Overall Survival	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.

Trial Locations

Locations (20)

Mayo Clinic - AZ; 🇺🇸 Scottsdale, Arizona, United States

Christiana Care Health Services, Inc.; 🇺🇸 Newark, Delaware, United States

Mayo Clinic - FL; 🇺🇸 Jacksonville, Florida, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Norton Cancer Institute Research Program; 🇺🇸 Louisville, Kentucky, United States

University of Maryland Greenbaum Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

South Texas Accelerated Research Therapeutics, LLC - Midwest; 🇺🇸 Grand Rapids, Michigan, United States

Mayo Clinic - MN; 🇺🇸 Rochester, Minnesota, United States

Nebraska Cancer Specialists; 🇺🇸 Omaha, Nebraska, United States

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