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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02475213
Recruitment Status : Completed
First Posted : June 18, 2015
Last Update Posted : September 28, 2021
Sponsor:
Information provided by (Responsible Party):
MacroGenics

Tracking Information
First Submitted Date  ICMJE June 16, 2015
First Posted Date  ICMJE June 18, 2015
Last Update Posted Date September 28, 2021
Actual Study Start Date  ICMJE July 2015
Actual Primary Completion Date August 18, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2015)
Number of participants with adverse events [ Time Frame: one year ]
Adverse Events, Serious Adverse Events
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2021)
  • Peak plasma concentration [ Time Frame: 7 weeks ]
    PK of MGA271 in combination with pembrolizumab
  • Number of participants that develop anti-drug antibodies [ Time Frame: One year ]
    Proportion of patients who develop anti-MGA271 antibodies, immunogenicity
  • Change in tumor volume RECIST 1.1 criteria [ Time Frame: Weeks 6, 15, 24, 33, 42, 51 ]
    Anti-tumor activity of MGA271 in combination with pembrolizumab and in combination with MGA012 using both conventional RECIST 1.1.
  • Change in tumor volume using immune-related RECIST criteria [ Time Frame: Weeks 6, 15, 24, 33, 42, 51 ]
    Anti-tumor activity of MGA271 in combination with pembrolizumab and in combination with MGA012 using immune-related RECIST criteria.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2015)
  • Peak plasma concentration [ Time Frame: 7 weeks ]
    PK of MGA271 in combination with pembrolizumab
  • Number of participants that develop anti-drug antibodies [ Time Frame: One year ]
    Proportion of patients who develop anti-MGA271 antibodies, immunogenicity
  • Change in tumor volume [ Time Frame: Weeks 6, 15, 24, 33, 42, 51 ]
    Anti-tumor activity of MGA271 in combination with pembrolizumab using both conventional RECIST 1.1 and immune-related RECIST criteria.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab or MGA012 in Refractory Cancer
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Melanoma
  • Head and Neck Cancer
  • Non Small Cell Lung Cancer
  • Urethelial Carcinoma
Intervention  ICMJE
  • Biological: Enoblituzumab
    enoblituzumab is administered by IV infusion once per week for up to 51 doses.
    Other Name: MGA271
  • Biological: Pembrolizumab
    Pembrolizumab is administered by IV infusion every 3 weeks for up to 17 doses.
    Other Name: Keytruda
  • Biological: MGA012
    anti-PD-1 monoclonal antibody
    Other Name: INCMGA00012
Study Arms  ICMJE
  • Experimental: Cohort 1: enoblituzumab 3 mg/kg plus pembrolizumab 2 mg/kg
    enoblituzumab 3 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
    Interventions:
    • Biological: Enoblituzumab
    • Biological: Pembrolizumab
  • Experimental: Cohort 2: enoblituzumab 10 mg/kg plus pembrolizumab 2 mg/kg
    enoblituzumab 10 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
    Interventions:
    • Biological: Enoblituzumab
    • Biological: Pembrolizumab
  • Experimental: Cohort 3: enoblituzumab 15 mg/kg plus pembrolizumab 2 mg/kg
    enoblituzumab 15 mg/kg IV weekly plus pembrolizumab 2 mg/kg IV every 3 weeks
    Interventions:
    • Biological: Enoblituzumab
    • Biological: Pembrolizumab
  • Experimental: Cohort 4: enoblituzumab 15 mg/kg plus MGA012 375 mg
    enoblituzumab 15 mg/kg IV weekly plus MGA012 375 mg
    Interventions:
    • Biological: Enoblituzumab
    • Biological: MGA012
Publications * 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). pii: e004424. doi: 10.1136/jitc-2021-004424.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 21, 2020)
145
Original Estimated Enrollment  ICMJE
 (submitted: June 16, 2015)
75
Actual Study Completion Date  ICMJE August 18, 2021
Actual Primary Completion Date August 18, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02475213
Other Study ID Numbers  ICMJE CP-MGA271-03
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party MacroGenics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE MacroGenics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Chet Bohac, PharmD MD MSc MacroGenics
PRS Account MacroGenics
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP