Head and Neck Cancer, Squamous Cell Carcinoma of Head and Neck
Conditions
Keywords
SCCHN, head and neck, oropharyngeal, oral cavity, hypopharyngeal, laryngeal cancer, immunotherapy, PD-1, B7-H3, LAG-3
Brief summary
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
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).
Interventions
BIOLOGICALenoblituzumab
anti-B7-H3 antibody
BIOLOGICALMGA012
anti-PD-1 antibody
BIOLOGICALMGD013
PD-1 X LAG-3 bispecific DART protein
Sponsors
MacroGenics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel study model refers to concurrent enrollment of non-randomized Modules X and Y.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (Modules X and Y) | 2 years | Proportion of patients with best overall response of complete response (CR) plus partial response (PR) per RECIST 1.1 |
| Incidence of Adverse Events as assessed by CTCAE v 4.03 (Modules X and Y) | Up to 30 days after last dose of study drug | Evaluation of adverse events and serious adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate - (Modules X and Y) | 2 years | Percentage of patients who experienced response of CR, PR or stable disease for at least 3 months from start of study treatment |
| Immunogenicity (Module X) | 2 years | Percentage of patients developing anti-drug antibodies to enoblituzumab and/or MGA012 |
| Immunogenicity (Module Y) | 2 years | Percentage of patients developing anti-drug antibodies to enoblituzumab and/or MGD013 |
| Duration of Response - (Modules X and Y) | 2 years | Time from the date of initial response to the date of first documented progression or death from any cause, whichever occurs first |
| Ctrough (Module X) | 2 years | Trough serum concentration of enoblituzumab and MGA012 |
| Cmax (Module Y) | 2 years | Maximum serum concentration of enoblituzumab and MGD013 |
| Ctrough (Module Y) | 2 years | Trough serum concentration of enoblituzumab and MGD013 |
| Cmax (Module X) | 2 years | Maximum serum concentration of enoblituzumab and MGA012 |
| Progression-free Survival - (Modules X and Y) | 2 years | 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. |
Outcome results
None listed