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

Sponsor

MacroGenics (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT04129320

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer Squamous Cell Carcinoma of Head and Neck	Biological: enoblituzumab Biological: MGA012 Biological: MGD013	Phase 2/Phase 3

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel study model refers to concurrent enrollment of non-randomized Modules X and Y.Parallel study model refers to concurrent enrollment of non-randomized Modules X and Y.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Oct 1, 2019

Anticipated Primary Completion Date :

Oct 1, 2020

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Arm 1 Enoblituzumab plus MGA012	Biological: enoblituzumab anti-B7-H3 antibody Other Names: MGA271 Biological: MGA012 anti-PD-1 antibody Other Names: INCMGA00012
Experimental: Experimental Arm 2 Enoblituzumab plus MGD013	Biological: enoblituzumab anti-B7-H3 antibody Other Names: MGA271 Biological: MGD013 PD-1 X LAG-3 bispecific DART protein

Arm

Intervention/Treatment

Experimental: Experimental Arm 1

Enoblituzumab plus MGA012

Biological: enoblituzumab

anti-B7-H3 antibody

Other Names:

MGA271

Biological: MGA012

anti-PD-1 antibody

Other Names:

INCMGA00012

Experimental: Experimental Arm 2

Enoblituzumab plus MGD013

Biological: enoblituzumab

anti-B7-H3 antibody

Other Names:

MGA271

Biological: MGD013

PD-1 X LAG-3 bispecific DART protein

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.
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
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
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
Cmax (Module X) [2 years]
Maximum serum concentration of enoblituzumab and MGA012
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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