Back to resultsEnoblituzumab Plus Retifanlimab or Tebotelimab in Head and Neck Cancer
Primary Purpose
Head and Neck Cancer, Head and Neck Neoplasms, Head and Neck Squamous Cell Carcinoma
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Enoblituzumab
Retifanlimab
Tebotelimab
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Cancer
Eligibility Criteria
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
- Positive (combined positive score [CPS] ≥ 1) for the retifanlimab cohort, or
- 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
Sites / Locations
- University of Maryland, Greenebaum Comprehensive Cancer Center
- University of Michigan
- Comprehensive Cancer Centers of Nevada
- University of North Carolina - Lineberger Cancer Center
- University of Pennsylvania - Abramson Cancer Center
- University of Pittsburgh Medical Center- Hillman Cancer Center
- Liverpool Hospital
- Monash Health, Medical Oncology Department
- Royal North Shore Hospital
- Calvary Mater Newcastle
- Icon Cancer Centre Southport
- Andrew Love Cancer Centre, Barwon Health
- Fiona Stanley Hospital
- Complex Oncology Center Ruse Ltd.
- MHAT Serdica
- MBAL Uni Hospital
- MHAT Nadezhda, Medical Oncology
- UMHAT Tsarisa Yoanna - ISUL
- UMHAT Georgi Stranski Medical Oncology Department
- COC Dobrich
- Bajcsy-Zsilinszky Korhaz
- Uzsoki Street Hospital
- Dept of Oncology, University of Debrecen
- Dept of Oncology, Bekec County Hosp
- Dept of Oncology, Tolna County Hospital
- The Ewa Pilecka Department of Clinical Oncology
- Uniwersyteckie Centrum Kliniczne
- I Clinics of Radiotherapy and Chemiotherapy; The Maria Sklodowska-Curie National Research Institute of Oncology
- Biokinetica
- Clinics of Head and Neck Cancer, The Maria Sklodowska-Curie National Research Institute of Oncology
- Complejo Hospitalario Universitario de Badajoz
- Hospital Universitario Vall D'Hebrón
- Hospital Clínic de Barcelona
- Hospital Clínico San Carlos
- Clinica Universidad de Navarra
- Hospital Universitario Virgen de la Macarena
- Communal Non-profit Enterprise "City Clinical Hospital#4" of Dnipro City
- Communal Non-Profit Enterprise "Regional Center of Oncology", Oncosurgical Department of Head and Neck
- Communal Non-profit Enterprise "Regional Clinical Oncology Center of Kirovohrad Regional Council",
- Kyiv City Clinical Oncological Centre
- Municipal Non-Profit Enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Dispensary"
- Communal Nonprofit Enterprise Podilsky Regional Center of Oncology
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Retifanlimab Cohort
Tebotelimab Cohort
Arm Description
Enoblituzumab 15 mg/kg every 3 weeks plus retifanlimab 375 mg every 3 weeks for up to 35 cycles
Enoblituzumab 15 mg/kg every 3 weeks plus tebotelimab 600 mg every 3 weeks for up to 35 cycles
Outcomes
Primary Outcome Measures
Overall Response Rate (ORR) of enoblituzumab plus retifanlimab
Investigator-assessed ORR. defined as the proportion of patients in the response evaluable population who achieve the best overall response of complete response (CR) or partial response (PR).
Number of patients with AEs receiving enoblituzumab plus tebotelimab
Incidence of treatment-emergent adverse events
ORR of enoblituzumab plus tebotelimab
Investigator-assessed ORR. ORR, defined as the proportion of patients in the response evaluable population who achieve the a best overall response of complete response (CR) or partial response (PR).
Secondary Outcome Measures
Progression-free survival
Time from the first dose date to the date of first documented progression or death from any cause, whichever occurs first, evaluated by cohort
Disease-control rate
Percentage of response-evaluable patients with CR, PR, or stable disease (SD) for at least 3 months, evaluated by cohort
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
Overall survival
Time from the first dose date to the date of death from any cause, evaluated by cohort
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)
Number of patients with AEs receiving enoblituzumab plus retifanlimab
Incidence of treatment-emergent adverse events
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.
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.
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.
Trough concentration of enoblituzumab (Ctrough or Cmin)
The amount of tebotelimab left in the bloodstream before the next dose is given.
Trough concentration of tebotelimab (Ctrough or Cmin)
The amount of tebotelimab left in the bloodstream before the next dose is given.
Trough concentration of retifanlimab (Ctrough or Cmin)
The amount of retifanlimab left in the bloodstream before the next dose is given.
Number of patients who develop antidrug antibodies (ADA) to enoblituzumab.
Number of patients who develop ADA to tebotelimab
Proportion of patients who develop anti-drug antibodies to enoblituzumab or retifanlimab
Number of patients who ADA to retifanlimab
Proportion of patients who develop anti-drug antibodies to enoblituzumab or tebotelimab.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04634825
Brief Title
Enoblituzumab Plus Retifanlimab or Tebotelimab in Head and Neck Cancer
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Terminated
Why Stopped
Based on internal review of safety data
Study Start Date
March 17, 2021 (Actual)
Primary Completion Date
July 29, 2022 (Actual)
Study Completion Date
July 29, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MacroGenics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer, Head and Neck Neoplasms, Head and Neck Squamous Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Enrollment into each cohort will occur independently in a non-randomized fashion, based on PD-L1 expression results. Patients may not crossover between cohorts.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
62 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Retifanlimab Cohort
Arm Type
Experimental
Arm Description
Enoblituzumab 15 mg/kg every 3 weeks plus retifanlimab 375 mg every 3 weeks for up to 35 cycles
Arm Title
Tebotelimab Cohort
Arm Type
Experimental
Arm Description
Enoblituzumab 15 mg/kg every 3 weeks plus tebotelimab 600 mg every 3 weeks for up to 35 cycles
Intervention Type
Biological
Intervention Name(s)
Enoblituzumab
Other Intervention Name(s)
MGA271
Intervention Description
Anti-B7-H3 antibody
Intervention Type
Biological
Intervention Name(s)
Retifanlimab
Other Intervention Name(s)
INCMGA00012, MGA012
Intervention Description
Anti-PD-1 antibody
Intervention Type
Biological
Intervention Name(s)
Tebotelimab
Other Intervention Name(s)
MGD013
Intervention Description
PD-1 X LAG-3 bispecific DART molecule
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR) of enoblituzumab plus retifanlimab
Description
Investigator-assessed ORR. defined as the proportion of patients in the response evaluable population who achieve the best overall response of complete response (CR) or partial response (PR).
Time Frame
Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 28 months.
Title
Number of patients with AEs receiving enoblituzumab plus tebotelimab
Description
Incidence of treatment-emergent adverse events
Time Frame
Throughout the study, up to 28 months.
Title
ORR of enoblituzumab plus tebotelimab
Description
Investigator-assessed ORR. ORR, defined as the proportion of patients in the response evaluable population who achieve the a best overall response of complete response (CR) or partial response (PR).
Time Frame
Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 28 months
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
Time from the first dose date to the date of first documented progression or death from any cause, whichever occurs first, evaluated by cohort
Time Frame
Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 28 months
Title
Disease-control rate
Description
Percentage of response-evaluable patients with CR, PR, or stable disease (SD) for at least 3 months, evaluated by cohort
Time Frame
Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 28 months
Title
Duration of response
Description
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
Time Frame
Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 28 months
Title
Overall survival
Description
Time from the first dose date to the date of death from any cause, evaluated by cohort
Time Frame
up to 28 months
Title
Best overall response (BOR)
Description
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)
Time Frame
Tumor assessment is conducted 6 weeks after first dose, then every 9 weeks until disease progression, up to 28 months
Title
Number of patients with AEs receiving enoblituzumab plus retifanlimab
Description
Incidence of treatment-emergent adverse events
Time Frame
Throughout the study, up to 28 months.
Title
Maximum drug concentration or drug concentration of enoblituzumab at the end of infusion of enoblituzumab (Cmax)
Description
The highest measured concentration of enoblituzumab in the bloodstream.
Time Frame
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
Title
Maximum drug concentration or drug concentration of tebotelimab at the end of infusion of tebotelimab (Cmax)
Description
The highest measured concentration of tebotelimab in the bloodstream.
Time Frame
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
Title
Maximum drug concentration or drug concentration of retifanlimab at the end of infusion of enoblituzumab (Cmax)
Description
The highest measured concentration of retifanlimab in the bloodstream.
Time Frame
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
Title
Trough concentration of enoblituzumab (Ctrough or Cmin)
Description
The amount of tebotelimab left in the bloodstream before the next dose is given.
Time Frame
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
Title
Trough concentration of tebotelimab (Ctrough or Cmin)
Description
The amount of tebotelimab left in the bloodstream before the next dose is given.
Time Frame
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
Title
Trough concentration of retifanlimab (Ctrough or Cmin)
Description
The amount of retifanlimab left in the bloodstream before the next dose is given.
Time Frame
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
Title
Number of patients who develop antidrug antibodies (ADA) to enoblituzumab.
Time Frame
Prior to treatment and at the beginning of every 3-week cycle of treatment up to 28 months
Title
Number of patients who develop ADA to tebotelimab
Description
Proportion of patients who develop anti-drug antibodies to enoblituzumab or retifanlimab
Time Frame
Prior to treatment and at the beginning of every 3-week cycle of treatment up to 28 months
Title
Number of patients who ADA to retifanlimab
Description
Proportion of patients who develop anti-drug antibodies to enoblituzumab or tebotelimab.
Time Frame
Prior to treatment and at the beginning of every 3-week cycle of treatment up to 28 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Positive (combined positive score [CPS] ≥ 1) for the retifanlimab cohort, or
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ashley L. Ward, MD
Organizational Affiliation
MacroGenics
Official's Role
Study Director
Facility Information:
Facility Name
University of Maryland, Greenebaum Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
University of North Carolina - Lineberger Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
University of Pennsylvania - Abramson Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh Medical Center- Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Liverpool Hospital
City
Liverpool
State/Province
New South Wales
ZIP/Postal Code
2170
Country
Australia
Facility Name
Monash Health, Medical Oncology Department
City
Ruse
State/Province
New South Wales
ZIP/Postal Code
3168
Country
Australia
Facility Name
Royal North Shore Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Calvary Mater Newcastle
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
Icon Cancer Centre Southport
City
Southport
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
Facility Name
Andrew Love Cancer Centre, Barwon Health
City
Geelong
State/Province
Victoria
ZIP/Postal Code
3220
Country
Australia
Facility Name
Fiona Stanley Hospital
City
Murdoch
State/Province
Western Australia
ZIP/Postal Code
6150
Country
Australia
Facility Name
Complex Oncology Center Ruse Ltd.
City
Dobrich
ZIP/Postal Code
7002
Country
Bulgaria
Facility Name
MHAT Serdica
City
Panagyurishte
ZIP/Postal Code
1632
Country
Bulgaria
Facility Name
MBAL Uni Hospital
City
Pleven
ZIP/Postal Code
4500
Country
Bulgaria
Facility Name
MHAT Nadezhda, Medical Oncology
City
Sofia
ZIP/Postal Code
1373
Country
Bulgaria
Facility Name
UMHAT Tsarisa Yoanna - ISUL
City
Sofia
ZIP/Postal Code
1527
Country
Bulgaria
Facility Name
UMHAT Georgi Stranski Medical Oncology Department
City
Sofia
ZIP/Postal Code
5800
Country
Bulgaria
Facility Name
COC Dobrich
City
Sofia
ZIP/Postal Code
9300
Country
Bulgaria
Facility Name
Bajcsy-Zsilinszky Korhaz
City
Budapest
ZIP/Postal Code
01106
Country
Hungary
Facility Name
Uzsoki Street Hospital
City
Budapest
ZIP/Postal Code
1145
Country
Hungary
Facility Name
Dept of Oncology, University of Debrecen
City
Debrecen
ZIP/Postal Code
04032
Country
Hungary
Facility Name
Dept of Oncology, Bekec County Hosp
City
Gyula
ZIP/Postal Code
5700
Country
Hungary
Facility Name
Dept of Oncology, Tolna County Hospital
City
Szekszard
ZIP/Postal Code
7100
Country
Hungary
Facility Name
The Ewa Pilecka Department of Clinical Oncology
City
Bialystok
ZIP/Postal Code
15027
Country
Poland
Facility Name
Uniwersyteckie Centrum Kliniczne
City
Gdańsk
ZIP/Postal Code
80-214
Country
Poland
Facility Name
I Clinics of Radiotherapy and Chemiotherapy; The Maria Sklodowska-Curie National Research Institute of Oncology
City
Gliwice
ZIP/Postal Code
44-102
Country
Poland
Facility Name
Biokinetica
City
Jozefow
ZIP/Postal Code
05-410
Country
Poland
Facility Name
Clinics of Head and Neck Cancer, The Maria Sklodowska-Curie National Research Institute of Oncology
City
Warszawa
Country
Poland
Facility Name
Complejo Hospitalario Universitario de Badajoz
City
Badajoz
ZIP/Postal Code
06080
Country
Spain
Facility Name
Hospital Universitario Vall D'Hebrón
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clínic de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Clínico San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Clinica Universidad de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital Universitario Virgen de la Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Communal Non-profit Enterprise "City Clinical Hospital#4" of Dnipro City
City
Dnipro
ZIP/Postal Code
49102
Country
Ukraine
Facility Name
Communal Non-Profit Enterprise "Regional Center of Oncology", Oncosurgical Department of Head and Neck
City
Kharkiv
ZIP/Postal Code
61070
Country
Ukraine
Facility Name
Communal Non-profit Enterprise "Regional Clinical Oncology Center of Kirovohrad Regional Council",
City
Kropyvnytskyi
ZIP/Postal Code
25000
Country
Ukraine
Facility Name
Kyiv City Clinical Oncological Centre
City
Kyiv
ZIP/Postal Code
03115
Country
Ukraine
Facility Name
Municipal Non-Profit Enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Dispensary"
City
Sumy
ZIP/Postal Code
40022
Country
Ukraine
Facility Name
Communal Nonprofit Enterprise Podilsky Regional Center of Oncology
City
Vinnytsia
ZIP/Postal Code
21029
Country
Ukraine
12. IPD Sharing Statement
Plan to Share IPD
No
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Enoblituzumab Plus Retifanlimab or Tebotelimab in Head and Neck Cancer
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