Enoblituzumab Plus MGA012 or MGD013 in Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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This is an open-label study designed to evaluate safety and efficacy of enoblituzumab in combination with MGA012 or MGD013 in first-line treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).

Detailed Description
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The study will initially be conducted in 2 modules, Module X (enoblituzumab plus MGA012) and Module Y (enoblituzumab plus MGD013). Enrollment into Modules X and Y, with approximately 30 patients each, will occur independently in a non-randomized fashion. Data from these modules will determine if further evaluation will occur in randomized Module A (Phase 2) and randomized Module B (Phase 3).

Official Title
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A Phase 2/3 Open-Label Trial to Evaluate Enoblituzumab in Combination With MGA012 or MGD013 in the First-Line Treatment of Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Conditions
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Head and Neck Cancer, Squamous Cell Carcinoma of Head and Neck

Intervention / Treatment
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* Biological: enoblituzumab
* Biological: MGA012
* Biological: MGD013


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven, recurrent or metastatic SCCHN not curable by local therapy No prior systemic therapy for SCCHN in the recurrent or metastatic setting (with the exception of systemic therapy completed > 6 months prior of given as part of multimodal treatment for locally advanced disease) Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx At least one radiographically measurable lesion HPV test results available (positive and negative eligible) ECOG Performance status of 0 or 1 Adequate end organ function Positive PD-L1 expression level (CPS ≥ 1%) Exclusion Criteria: Disease suitable for local therapy administered with curative intent Progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced SCCHN Radiation or other non-systemic therapy within 2 weeks of first dose of study drug Diagnosis of immunodeficiency, or use of immunosuppresive therapy within 14 days of first dose of study drug

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel study model refers to concurrent enrollment of non-randomized Modules X and Y.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm 1<br>Enoblituzumab plus MGA012 | Biological: enoblituzumab<br>* anti-B7-H3 antibody<br>* Other names: MGA271;Biological: MGA012<br>* anti-PD-1 antibody<br>* Other names: INCMGA00012;|
| Experimental: Experimental Arm 2<br>Enoblituzumab plus MGD013 | Biological: enoblituzumab<br>* anti-B7-H3 antibody<br>* Other names: MGA271;Biological: MGD013<br>* PD-1 X LAG-3 bispecific DART protein<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (Modules X and Y) | Proportion of patients with best overall response of complete response (CR) plus partial response (PR) per RECIST 1.1 | 2 years | 
| Incidence of Adverse Events as assessed by CTCAE v 4.03 (Modules X and Y) | Evaluation of adverse events and serious adverse events | Up to 30 days after last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival - (Modules X and Y) | Time from start of study treatment to the first documented disease progression per RECIST v1.1 or death due to any cause, whichever occurs first. | 2 years | 
| Disease Control Rate - (Modules X and Y) | Percentage of patients who experienced response of CR, PR or stable disease for at least 3 months from start of study treatment | 2 years | 
| Duration of Response - (Modules X and Y) | Time from the date of initial response to the date of first documented progression or death from any cause, whichever occurs first | 2 years | 
| Immunogenicity (Module X) | Percentage of patients developing anti-drug antibodies to enoblituzumab and/or MGA012 | 2 years | 
| Immunogenicity (Module Y) | Percentage of patients developing anti-drug antibodies to enoblituzumab and/or MGD013 | 2 years | 
| Cmax (Module X) | Maximum serum concentration of enoblituzumab and MGA012 | 2 years | 
| Ctrough (Module X) | Trough serum concentration of enoblituzumab and MGA012 | 2 years | 
| Cmax (Module Y) | Maximum serum concentration of enoblituzumab and MGD013 | 2 years | 
| Ctrough (Module Y) | Trough serum concentration of enoblituzumab and MGD013 | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCCHN, head and neck, oropharyngeal, oral cavity, hypopharyngeal, laryngeal cancer, immunotherapy, PD-1, B7-H3, LAG-3