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

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Head and Neck Cancer; Squamous Cell Carcinoma of Head and Neck
• Intervention / Treatment: Biological: enoblituzumab; Biological: MGA012; Biological: MGD013

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 Type: Interventional
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: MacroGenics

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: October 14, 2019
• First Submitted That Met QC Criteria: October 15, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): February 8, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: immunotherapy; PD-1; LAG-3; head and neck; laryngeal cancer; SCCHN; B7-H3; oral cavity; oropharyngeal; hypopharyngeal
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: CP-MGA271-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No