Enoblituzumab Plus Retifanlimab or Tebotelimab in Head and Neck Cancer

A Phase 2 Open-Label Trial to Evaluate Enoblituzumab in Combination With Retifanlimab or Tebotelimab in the First-Line Treatment of Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

This is a Phase 2 study of enoblituzumab combined with either retifanlimab or tebotelimab administered as first-line treatment to patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Cancer; Head and Neck Neoplasms; Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Biological: Enoblituzumab; Biological: Retifanlimab; Biological: Tebotelimab

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • Ruse, New South Wales, Australia, 3168
      • Monash Health, Medical Oncology Department
    • Sydney, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Queensland
    • Southport, Queensland, Australia, 4215
      • ICON Cancer Centre Southport
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • Andrew Love Cancer Centre, Barwon Health
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Bulgaria
  • Dobrich, Bulgaria, 7002
    • Complex Oncology Center Ruse Ltd.
  • Panagyurishte, Bulgaria, 1632
    • MHAT Serdica
  • Pleven, Bulgaria, 4500
    • MBAL Uni Hospital
  • Sofia, Bulgaria, 1373
    • MHAT Nadezhda, Medical Oncology
  • Sofia, Bulgaria, 1527
    • UMHAT Tsarisa Yoanna - ISUL
  • Sofia, Bulgaria, 5800
    • UMHAT Georgi Stranski Medical Oncology Department
  • Sofia, Bulgaria, 9300
    • COC Dobrich
• Hungary
  • Budapest, Hungary, 01106
    • Bajcsy-Zsilinszky Kórház
  • Budapest, Hungary, 1145
    • Uzsoki Street Hospital
  • Debrecen, Hungary, 04032
    • Dept of Oncology, University of Debrecen
  • Gyula, Hungary, 5700
    • Dept of Oncology, Bekec County Hosp
  • Szekszard, Hungary, 7100
    • Dept of Oncology, Tolna County Hospital
• Poland
  • Bialystok, Poland, 15027
    • The Ewa Pilecka Department of Clinical Oncology
  • Gdańsk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Gliwice, Poland, 44-102
    • I Clinics of Radiotherapy and Chemiotherapy; The Maria Sklodowska-Curie National Research Institute of Oncology
  • Jozefow, Poland, 05-410
    • Biokinetica
  • Warszawa, Poland
    • Clinics of Head and Neck Cancer, The Maria Sklodowska-Curie National Research Institute of Oncology
• Spain
  • Badajoz, Spain, 06080
    • Complejo Hospitalario Universitario de Badajoz
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen De La Macarena
• Ukraine
  • Dnipro, Ukraine, 49102
    • Communal Non-profit Enterprise "City Clinical Hospital#4" of Dnipro City
  • Kharkiv, Ukraine, 61070
    • Communal Non-Profit Enterprise "Regional Center of Oncology", Oncosurgical Department of Head and Neck
  • Kropyvnytskyi, Ukraine, 25000
    • Communal Non-profit Enterprise "Regional Clinical Oncology Center of Kirovohrad Regional Council",
  • Kyiv, Ukraine, 03115
    • Kyiv City Clinical Oncological Centre
  • Sumy, Ukraine, 40022
    • Municipal Non-Profit Enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Dispensary"
  • Vinnytsia, Ukraine, 21029
    • Communal Nonprofit Enterprise Podilsky Regional Center of Oncology
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Greenebaum Comprehensive Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina - Lineberger Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania - Abramson Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center- Hillman Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically proven, recurrent or metastatic squamous cell carcinoma of the head and neck (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 if given as part of multimodal treatment for locally advanced disease)
• Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Patients may not have a primary tumor site of upper esophagus, salivary gland, or nasopharynx (any histology)
• Availability of formalin-fixed, paraffin embedded tumor specimen or contemporary biopsy for immunohistochemical evaluation of pharmacodynamic markers of interest
• Willing to consent for baseline and on-treatment biopsy.
• Performance status 0 or 1
• Life expectancy of 6 months or more
• Adequate end organ function
• At least one radiographically measurable lesion

• PD-L1 expression level that is either

  1. Positive (combined positive score [CPS] ≥ 1) for the retifanlimab cohort, or
  2. Negative (CPS < 1) for the tebotelimab cohort
• Results available from human papilloma virus p16 status for oropharyngeal cancer
• Acceptable laboratory results

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 prior to the first dose of study drug
• Prior therapy with an anti-B7-H3, anti-PD-1, anti-PD-L1, or anti-LAG-3 agent

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: Retifanlimab Cohort; Enoblituzumab 15 mg/kg every 3 weeks plus retifanlimab 375 mg every 3 weeks for up to 35 cycles	Biological: Enoblituzumab; Anti-B7-H3 antibody; Other Names: MGA271; Biological: Retifanlimab; Anti-PD-1 antibody; Other Names: INCMGA00012; MGA012; Zynyz
Experimental: Tebotelimab Cohort; Enoblituzumab 15 mg/kg every 3 weeks plus tebotelimab 600 mg every 3 weeks for up to 35 cycles	Biological: Enoblituzumab; Anti-B7-H3 antibody; Other Names: MGA271; Biological: Tebotelimab; PD-1 X LAG-3 bispecific DART molecule; Other Names: MGD013

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) of Enoblituzumab Plus Retifanlimab	Investigator-assessed ORR. defined as the percentage of patients in the response evaluable population who achieve the best overall response of complete response (CR) or partial response (PR),per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 criteria.. CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease from baseline in the sum of diameters of target lesions	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months.
Number of Patients With Adverse Events (AEs) Receiving Enoblituzumab Plus Tebotelimab		Throughout the study, up to 16.5 months.
ORR of Enoblituzumab Plus Tebotelimab	Investigator-assessed ORR. ORR, defined as the percentage of patients in the response evaluable population who achieve the a best overall response of complete response (CR) or partial response (PR), per RECIST, version 1.1 criteria. CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease from baseline in the sum of diameters of target lesions	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Time from the first dose date to the date of first documented progression or death from any cause, whichever occurs first, evaluated by cohort	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months
Disease-control Rate (DCR)	Percentage of response-evaluable patients with CR, PR, or stable disease (SD) for at least 3 months, evaluated by cohort	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months
Duration of Response	Time from the date of initial response (CR or PR) to the date of first documented progression or death from any cause, whichever occurs first, evaluated by cohort	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months
Overall Survival	Time from the first dose date to the date of death from any cause, evaluated by cohort	up to 16.5 months
Best Overall Response (BOR)	The participants best response to treatment during their study participation. Responses are categorized as CR, PR, stable disease (SD), progressive disease (PD), or not evaluated (NE), per RECIST 1.1 criteria CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease from baseline in the sum of diameters of target lesions, and non-PD in non-target lesions PD is defined as at least a 20% increase from nadir in the sum of diameters of target lesions or unequivocal progression in non-target lesions SD is defined as non-PD in target and non-target lesions	Tumor assessment is conducted 6 weeks after first dose, then every 9 weeks until disease progression, up to 16.5 months
Number of Patients With AEs Receiving Enoblituzumab Plus Retifanlimab		Throughout the study, up to 16.5 months.
Maximum Drug Concentration or Drug Concentration of Enoblituzumab at the End of Infusion of Enoblituzumab (Cmax)	The highest measured concentration of enoblituzumab in the bloodstream.	Cycle 1 Day 1: Pre-infusion, end of infusion (EOI [2 hours]), 4 hours after EOI; Cycle 1 Days 2, 3, 8 and 15 at any time; On Day 1 of Cycles 2, 3, 4, 5 and 6: Pre-infusion and EOI (each cycle is 21 days)
Maximum Drug Concentration or Drug Concentration of Tebotelimab at the End of Infusion of Tebotelimab (Cmax)	The highest measured concentration of tebotelimab in the bloodstream.	Cycle 1 Day 1: Pre-infusion, end of infusion (EOI [1 hour]), 4 hours after EOI; Cycle 1 Days 2, 3, 8 and 15 at any time; On Day 1 of Cycles 2, 3, 4, 5 and 6: Pre-infusion and EOI (each cycle is 21 days)
Maximum Drug Concentration or Drug Concentration of Retifanlimab at the End of Infusion of Enoblituzumab (Cmax)	The highest measured concentration of retifanlimab in the bloodstream.	Cycle 1 Day 1: Pre-infusion, end of infusion (EOI [1 hour]), 4 hours after EOI; Cycle 1 Days 2, 3, 8 and 15 at any time; On Day 1 of Cycles 2, 3, 4, 5 and 6: Pre-infusion and EOI (each cycle is 21 days)
Trough Concentration of Enoblituzumab (Ctrough or Cmin)	The amount of enoblituzumab left in the bloodstream before the next dose is given.	Cycle 1 Day 1: Pre-infusion, end of infusion (EOI [2 hours]), 4 hours after EOI; Cycle 1 Days 2, 3, 8 and 15 at any time; On Day 1 of Cycles 2, 3, 4, 5 and 6: Pre-infusion and EOI (each cycle is 21 days
Trough Concentration of Tebotelimab (Ctrough or Cmin)	The amount of tebotelimab left in the bloodstream before the next dose is given.	Cycle 1 Day 1: Pre-infusion, end of infusion (EOI [1 hour]), 4 hours after EOI; Cycle 1 Days 2, 3, 8 and 15 at any time; On Day 1 of Cycles 2, 3, 4, 5 and 6: Pre-infusion and EOI (each cycle is 21 days)
Trough Concentration of Retifanlimab (Ctrough or Cmin)	The amount of retifanlimab left in the bloodstream before the next dose is given.	Cycle 1 Day 1: Pre-infusion, end of infusion (EOI [1 hour]), 4 hours after EOI; Cycle 1 Days 2, 3, 8 and 15 at any time; On Day 1 of Cycles 2, 3, 4, 5 and 6: Pre-infusion and EOI (each cycle is 21 days)
Number of Patients Who Develop Antidrug Antibodies (ADA) to Enoblituzumab.		Prior to treatment (baseline) and at the beginning of every 3-week cycle of treatment (post baseline) up to 16.5 months
Number of Patients Who Develop ADA to Tebotelimab		Prior to treatment (baseline) and at the beginning of every 3-week cycle of treatment (post baseline) up to 16.5 months
Number of Patients Who ADA to Retifanlimab		Prior to treatment (baseline) and at the beginning of every 3-week cycle of treatment (post baseline) up to 16.5 months

Collaborators and Investigators

• Sponsor: MacroGenics
• Investigators: Study Director: Ashley L. Ward, MD, MacroGenics

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2021
• Primary Completion (Actual): July 29, 2022
• Study Completion (Actual): July 29, 2022

Study Registration Dates

• First Submitted: November 12, 2020
• First Submitted That Met QC Criteria: November 12, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Estimated): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: CP-MGA271-06

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