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

MacroGenics146 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

146

Conditions

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

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

...and 10 more locations

Outcomes

Primary Outcomes

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.

Time frame: Study Day 1-42, for Cohorts 1-4.

Secondary Outcomes

Mean Maximum Concentration of Enoblituzumab

The highest measured concentration of enoblizuzumab in the bloodstream.

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: At baseline, 1, 4, 24, and 72 and Day 7.

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

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

Number of Participants That Develop Retifanlimab ADA

Time frame: 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.

Time frame: 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.

Time frame: 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)