Clinical trial NCT04634825: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Head and Neck Cancer
Head and Neck Neoplasms
Head and Neck Squamous Cell Carcinoma
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
First posted: 2020-11-18
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.


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

  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

Primary outcomes:
measure: Overall Response Rate (ORR) of Enoblituzumab Plus Retifanlimab
timeFrame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months.
measure: Number of Patients With Adverse Events (AEs) Receiving Enoblituzumab Plus Tebotelimab
timeFrame: Throughout the study, up to 16.5 months.
measure: ORR of Enoblituzumab Plus Tebotelimab
timeFrame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months
measure: Disease-control Rate (DCR)
timeFrame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months
measure: Duration of Response
timeFrame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months
measure: Overall Survival
timeFrame: up to 16.5 months
measure: Best Overall Response (BOR)
timeFrame: Tumor assessment is conducted 6 weeks after first dose, then every 9 weeks until disease progression, up to 16.5 months
measure: Number of Patients With AEs Receiving Enoblituzumab Plus Retifanlimab
timeFrame: Throughout the study, up to 16.5 months.
measure: Maximum Drug Concentration or Drug Concentration of Enoblituzumab at the End of Infusion of Enoblituzumab (Cmax)
timeFrame: 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)
measure: Maximum Drug Concentration or Drug Concentration of Tebotelimab at the End of Infusion of Tebotelimab (Cmax)
timeFrame: 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)
measure: Maximum Drug Concentration or Drug Concentration of Retifanlimab at the End of Infusion of Enoblituzumab (Cmax)
timeFrame: 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)
measure: Trough Concentration of Enoblituzumab (Ctrough or Cmin)
timeFrame: 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
measure: Trough Concentration of Tebotelimab (Ctrough or Cmin)
timeFrame: 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)
measure: Trough Concentration of Retifanlimab (Ctrough or Cmin)
timeFrame: 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)
measure: Number of Patients Who Develop Antidrug Antibodies (ADA) to Enoblituzumab.
timeFrame: Prior to treatment (baseline) and at the beginning of every 3-week cycle of treatment (post baseline) up to 16.5 months
measure: Number of Patients Who Develop ADA to Tebotelimab
timeFrame: Prior to treatment (baseline) and at the beginning of every 3-week cycle of treatment (post baseline) up to 16.5 months
measure: Number of Patients Who ADA to Retifanlimab
timeFrame: Prior to treatment (baseline) and at the beginning of every 3-week cycle of treatment (post baseline) up to 16.5 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland, Greenebaum Comprehensive Cancer Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Chapel Hill
country: United States
facility: University of North Carolina - Lineberger Cancer Center
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania - Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center- Hillman Cancer Center
state: Pennsylvania
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Ruse
country: Australia
facility: Monash Health, Medical Oncology Department
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Southport
country: Australia
facility: Icon Cancer Centre Southport
state: Queensland
city: Geelong
country: Australia
facility: Andrew Love Cancer Centre, Barwon Health
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Dobrich
country: Bulgaria
facility: Complex Oncology Center Ruse Ltd.
city: Panagyurishte
country: Bulgaria
facility: MHAT Serdica
city: Pleven
country: Bulgaria
facility: MBAL Uni Hospital
city: Sofia
country: Bulgaria
facility: MHAT Nadezhda, Medical Oncology
city: Sofia
country: Bulgaria
facility: UMHAT Tsarisa Yoanna - ISUL
city: Sofia
country: Bulgaria
facility: UMHAT Georgi Stranski Medical Oncology Department
city: Sofia
country: Bulgaria
facility: COC Dobrich
city: Budapest
country: Hungary
facility: Bajcsy-Zsilinszky Korhaz
city: Budapest
country: Hungary
facility: Uzsoki Street Hospital
city: Debrecen
country: Hungary
facility: Dept of Oncology, University of Debrecen
city: Gyula
country: Hungary
facility: Dept of Oncology, Bekec County Hosp
city: Szekszard
country: Hungary
facility: Dept of Oncology, Tolna County Hospital
city: Bialystok
country: Poland
facility: The Ewa Pilecka Department of Clinical Oncology
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gliwice
country: Poland
facility: I Clinics of Radiotherapy and Chemiotherapy; The Maria Sklodowska-Curie National Research Institute of Oncology
city: Jozefow
country: Poland
facility: Biokinetica
city: Warszawa
country: Poland
facility: Clinics of Head and Neck Cancer, The Maria Sklodowska-Curie National Research Institute of Oncology
city: Badajoz
country: Spain
facility: Complejo Hospitalario Universitario de Badajoz
city: Barcelona
country: Spain
facility: Hospital Universitario Vall D'Hebrón
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de la Macarena
city: Dnipro
country: Ukraine
facility: Communal Non-profit Enterprise "City Clinical Hospital#4" of Dnipro City
city: Kharkiv
country: Ukraine
facility: Communal Non-Profit Enterprise "Regional Center of Oncology", Oncosurgical Department of Head and Neck
city: Kropyvnytskyi
country: Ukraine
facility: Communal Non-profit Enterprise "Regional Clinical Oncology Center of Kirovohrad Regional Council",
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Oncological Centre
city: Sumy
country: Ukraine
facility: Municipal Non-Profit Enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Dispensary"
city: Vinnytsia
country: Ukraine
facility: Communal Nonprofit Enterprise Podilsky Regional Center of Oncology
Study officials:
affiliation: MacroGenics
name: Ashley L. Ward, MD
role: STUDY_DIRECTOR
References: