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

Head and Neck Cancer Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02475213
• Other study ID #: CP-MGA271-03
• Status: Completed
• Phase: Phase 1
• Start date: July 2015
• Est. completion date: August 18, 2021

Study information

• Verified date: September 2021
• Source: MacroGenics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 145
• Est. completion date: August 18, 2021
• Est. primary completion date: August 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically-proven, unresectable, locally advanced or metastatic melanoma, SCCHN, NSCLC, and other cancers that express B7-H3.
• Melanoma that has progressed during or following at least 1 and up to 5 prior systemic treatments for unresectable locally advanced or metastatic disease, or melanoma patients who are intolerable of or have refused standard cancer therapy. Pre- and on-study biopsy required.
• SCCHN that has progressed during or following at least 1 and up to 5 prior systemic treatments for metastatic or recurrent disease deemed to be incurable. Patient who refuse radical resection for recurrent disease or are intolerant of or refused standard first line therapy are eligible to enroll
• NSCLC that has progressed during or following 1 - 5 prior systemic therapies for unresectable locally advanced or metastatic disease (at least one docetaxel, gemcitabine, or platinum analogue based therapy), or are intolerant of or refused standard cancer therapy. For squamous cell carcinoma, or adenocarcinoma without known activating mutation: the prior systemic therapy is at least one platinum analogue. For adenocarcinoma with known activating driver mutation: the prior systemic therapy is at least TKI directed
• Urothelial cancer arising in the bladder, renal pelvis, ureter or urethra that has progressed during or following at least 1 and up to 5 prior systemic treatments for unresectable locally advanced or metastatic disease (includes anti-PD-L1,anti-PD-1, but excludes other experimental therapies). Patients must have received at least one platinum-containing regimen (e.g., gemcitabine/cisplatin [GC], dose-dense methotrexate/vinblastine/doxorubicin/cisplatin [DDMVAC], or carboplatinum/gemcitabine). No more than 5 prior systemic regimens allowed.
• 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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Head and Neck Cancer
• Lung Neoplasms
• Melanoma
• Non Small Cell Lung Cancer
• Urethelial Carcinoma

Intervention

Biological:
• Enoblituzumab
enoblituzumab is administered by IV infusion once per week for up to 51 doses.
• Pembrolizumab
Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.
• MGA012
anti-PD-1 monoclonal antibody

Locations

Country	Name	City	State
United States	University of Maryland Greenbaum Cancer Center	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Gabrail Cancer Institute	Canton	Ohio
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	South Texas Accelerated Research Therapeutics, LLC - Midwest	Grand Rapids	Michigan
United States	Greenville Health System	Greenville	South Carolina
United States	Mayo Clinic - FL	Jacksonville	Florida
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Norton Cancer Institute Research Program	Louisville	Kentucky
United States	Columbia University Medical Center	New York	New York
United States	Christiana Care Health Services, Inc.	Newark	Delaware
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Hospital of the University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburg	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Mayo Clinic - MN	Rochester	Minnesota
United States	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas
United States	Mayo Clinic - AZ	Scottsdale	Arizona
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events	Adverse Events, Serious Adverse Events	one year
Secondary	Peak plasma concentration	PK of MGA271 in combination with pembrolizumab	7 weeks
Secondary	Number of participants that develop anti-drug antibodies	Proportion of patients who develop anti-MGA271 antibodies, immunogenicity	One year
Secondary	Change in tumor volume RECIST 1.1 criteria	Anti-tumor activity of MGA271 in combination with pembrolizumab and in combination with MGA012 using both conventional RECIST 1.1.	Weeks 6, 15, 24, 33, 42, 51
Secondary	Change in tumor volume using immune-related RECIST criteria	Anti-tumor activity of MGA271 in combination with pembrolizumab and in combination with MGA012 using immune-related RECIST criteria.	Weeks 6, 15, 24, 33, 42, 51