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

• ClinicalTrials.gov Identifier: NCT02475213
• Recruitment Status: Active, not recruiting
• First Posted: June 18, 2015
• Last Update Posted: April 14, 2021
• Sponsor: MacroGenics
• Information provided by (Responsible Party): MacroGenics

Tracking Information

• First Submitted Date: June 16, 2015
• First Posted Date: June 18, 2015
• Last Update Posted Date: April 14, 2021
• Actual Study Start Date: July 2015
• Estimated Primary Completion Date: October 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 16, 2015)

Number of participants with adverse events [ Time Frame: one year ]

Adverse Events, Serious Adverse Events

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 15, 2019)

• 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 and in combination with MGA012 using both conventional RECIST 1.1 and immune-related RECIST criteria.

Original Secondary Outcome Measures (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: 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
• 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

This study is a Phase 1 open-label, dose escalation, cohort expansion, and efficacy follow-up study of enoblituzumab administered intravenously (IV) on a weekly schedule for up to 51 doses in combination with IV pembrolizumab administered on an every-3-week schedule for up to 17 doses.

The dose escalation phase is designed to characterize the safety and tolerability of the combination of enoblituzumab and pembrolizumab and to define the maximum tolerated or maximum administered dose (MTD/MAD). Patients with methothelioma, urethelial cancer, NSCLC, SCCHN, clear cell renal cell carcinoma (ccRCC), ovarian cancer, melanoma, thyroid cancer, triple negative breast cancer (TBNC), pancreatic cancer, colon cancer, soft tissue sarcoma, or prostate cancer will be enrolled in this study phase. An additional dose escalation cohort of up to 15 patients is designed to characterize the safety and tolerability of the combination of enoblituzumab and MGA012 in patients with melanoma, SCCHN, NSCLC, urothelial cancer, and other cancers, and any dose level not exceeding the MTD may be expanded to further evaluate safety and efficacy of this combination.

During the Cohort Expansion Phase, additional cohorts of patients with B7-H3 expressing unresectable, locally-advanced or metastatic melanoma (up to n=16), 2 cohorts of NSCLC (n= up to 20 in each cohort), 2 cohorts of SCCHN (up to n=20 in each cohort) or urothelial cancer (up to n=16) will be enrolled to receive MGA271 in combination with pembrolizumab at the MTD (or MAD) established from the Dose Escalation Phase of the study.

The efficacy follow-up period consists of the 2-year period after the final dose of study drug.

All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid Tumors (RECIST) and immune-related response criteria (irRC).

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• 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

• Experimental: enoblituzumab plus pembrolizumab
  Enoblituzumab: Fc-optimized, humanized monoclonal antibody. Pembrolizumab: Keytruda; human programmed death receptor-1 (PD-1)-blocking antibody approved by the US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor, or with advanced (metastatic) non-small cell lung cancer (NSCLC) whose disease has progressed after other treatments and with tumors that express a protein called PD-L1. Keytruda is approved for use with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, the first test designed to detect PD-L1 expression in non-small cell lung tumors.
  Interventions:

  • Biological: Enoblituzumab
  • Biological: Pembrolizumab
• Experimental: enoblituzumb plus MGA012
  Enoblituzumab: Fc-optimized, humanized monoclonal antibody. MGA012: anti-PD-1 monoclonal antibody.
  Interventions:

  • Biological: Enoblituzumab
  • Biological: MGA012

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 21, 2020): 145
• Original Estimated Enrollment (submitted: June 16, 2015): 75
• Estimated Study Completion Date: October 2022
• Estimated Primary Completion Date: October 2021 (Final data collection date for primary outcome measure)

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 chilhood 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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02475213
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Responsible Party: MacroGenics
• Study Sponsor: MacroGenics
• Collaborators: Not Provided

Investigators

• Study Director: Stacie Goldberg, M.D.; MacroGenics

• PRS Account: MacroGenics
• Verification Date: April 2021