Clinical trial NCT02475213: Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab or MGA012 in Refractory Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Head and Neck Cancer
Non Small Cell Lung Cancer
Urethelial Carcinoma
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
First posted: 2015-06-18
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: one year
Secondary outcomes:
measure: Peak plasma concentration
timeFrame: 7 weeks
measure: Number of participants that develop anti-drug antibodies
timeFrame: One year
measure: Change in tumor volume RECIST 1.1 criteria
timeFrame: Weeks 6, 15, 24, 33, 42, 51
measure: Change in tumor volume using immune-related RECIST criteria
timeFrame: Weeks 6, 15, 24, 33, 42, 51
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic - AZ
state: Arizona
city: Newark
country: United States
facility: Christiana Care Health Services, Inc.
state: Delaware
city: Jacksonville
country: United States
facility: Mayo Clinic - FL
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Louisville
country: United States
facility: Norton Cancer Institute Research Program
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Greenbaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Grand Rapids
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC - Midwest
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - MN
state: Minnesota
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Institute
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburg
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
Study officials:
affiliation: MacroGenics
name: Chet Bohac, PharmD MD MSc
role: STUDY_DIRECTOR
References:
citation: 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.