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OpenTrials
Completed

NCT Number: NCT02475213

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

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.

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Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Enoblituzumab Schedule 1

Biological

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

Other names: MGA271

Pembrolizumab

Biological

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

Other names: Keytruda

Enoblituzumab Schedule 2

Biological

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

Other names: MGA271

Retifanlimab

Biological

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

Other names: INCMGA00012, MGA012

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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

  7. Number of Participants That Develop Enoblituzumab Anti-drug Antibodies (ADA)

    Time frame: Every 3 weeks throughout the study, average duration 13 months.

  8. Number of Participants That Develop Retifanlimab ADA

    Time frame: Every 3 weeks throughout the study, average duration 13 months.

  9. 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.

  10. 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.

  11. 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)

  12. 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)

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

Sponsors and collaborators

Lead sponsor

MacroGenics

Industry

Registry information

Official study title

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

Important dates

Study start
2015
Primary completion
2021
Study completion
2021
First posted
Jun 18, 2015
Registry last updated
Aug 11, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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