Enoblituzumab Plus Retifanlimab or Tebotelimab in Head and Neck Cancer

• ClinicalTrials.gov Identifier: NCT04634825
• Recruitment Status: Recruiting
• First Posted: November 18, 2020
• Last Update Posted: May 18, 2022
• Sponsor: MacroGenics
• Information provided by (Responsible Party): MacroGenics

Tracking Information

• First Submitted Date: November 12, 2020
• First Posted Date: November 18, 2020
• Last Update Posted Date: May 18, 2022
• Actual Study Start Date: March 17, 2021
• Estimated Primary Completion Date: April 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 12, 2020)

• Efficacy of enoblituzumab plus retifanlimab [ Time Frame: 28 months ]
  Investigator-assessed objective response rate (complete response [CR] or partial response [PR])
• Safety of enoblituzumab plus tebotelimab [ Time Frame: 30 days after last dose ]
  Incidence of treatment-emergent adverse events
• Efficacy of enoblituzumab plus tebotelimab [ Time Frame: 28 months ]
  Investigator-assessed objective response rate

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 7, 2021)

• Progression-free survival [ Time Frame: 28 months ]
  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 [ Time Frame: 28 months ]
  Percentage of response-evaluable patients with CR, PR, or stable disease (SD) for at least 3 months, evaluated by cohort
• Duration of response [ Time Frame: 28 months ]
  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 Frame: 28 months ]
  Time from the first dose date to the date of death from any cause, evaluated by cohort
• Safety of enoblituzumab plus retifanlimab [ Time Frame: 30 days after last dose ]
  Incidence of treatment-emergent adverse events
• Pharmacokinetics of enoblituzumab plus retifanlimab [ Time Frame: up to 42 weeks ]
  Serum concentration of enoblituzumab and retifanlimab
• Pharmacokinetics of enoblituzumab plus tebotelimab [ Time Frame: up to 42 weeks ]
  Serum concentration of enoblituzumab and tebotelimab
• Immunogenicity of enoblituzumab or retifanlimab [ Time Frame: 28 months ]
  Proportion of patients who develop anti-drug antibodies to enoblituzumab or retifanlimab
• Immunogenicity of enoblituzumab or tebotelimab [ Time Frame: 28 months ]
  Proportion of patients who develop anti-drug antibodies to enoblituzumab or tebotelimab.

Original Secondary Outcome Measures (submitted: November 12, 2020)

• Progression-free survival [ Time Frame: 28 months ]
  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 [ Time Frame: 28 months ]
  Percentage of response-evaluable patients with CR, PR, or stable disease (SD) for at least 3 months, evaluated by cohort
• Duration of response [ Time Frame: 28 months ]
  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 Frame: 28 months ]
  Time from the first dose date to the date of death from any cause, evaluated by cohort
• Safety of enoblituzumab plus retifanlimab [ Time Frame: 30 days after last dose ]
  Incidence of treatment-emergent adverse events
• Pharmacokinetics of enoblituzumab plus retifanlimab [ Time Frame: up to 42 weeks ]
  Serum concentration of enoblituzumab and retifanlimab
• Pharmacokinetics of enoblituzumab plus tebotelimab [ Time Frame: up to 42 weeks ]
  Serum concentration of enoblituzumab and tebotelimab
• Immunogenicity of enoblituzumab plus retifanlimab [ Time Frame: 28 months ]
  Proportion of patients who develop anti-drug antibodies
• Immunogenicity of enoblituzumab plus tebotelimab [ Time Frame: 28 months ]
  Proportion of patients who develop anti-drug antibodies

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
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.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Head and Neck Cancer
• Head and Neck Neoplasms
• Head and Neck Squamous Cell Carcinoma

Intervention

• Biological: Enoblituzumab
  Anti-B7-H3 antibody
  Other Name: MGA271
• Biological: Retifanlimab
  Anti-PD-1 antibody
  Other Name: INCMGA00012, MGA012
• Biological: Tebotelimab
  PD-1 X LAG-3 bispecific DART molecule
  Other Name: MGD013

Study Arms

• Experimental: Retifanlimab Cohort
  Enoblituzumab 15 mg/kg every 3 weeks plus retifanlimab 375 mg every 3 weeks for up to 35 cycles
  Interventions:

  • Biological: Enoblituzumab
  • Biological: Retifanlimab
• Experimental: Tebotelimab Cohort
  Enoblituzumab 15 mg/kg every 3 weeks plus tebotelimab 600 mg every 3 weeks for up to 35 cycles
  Interventions:

  • Biological: Enoblituzumab
  • Biological: Tebotelimab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 12, 2020): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2024
• Estimated Primary Completion Date: April 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Global Trial Manager; 301-251-5172; info@macrogenics.com

• Listed Location Countries: Australia, Bulgaria, Hungary, Poland, Spain, Ukraine, United States

Administrative Information

• NCT Number: NCT04634825
• Other Study ID Numbers: CP-MGA271-06
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: MacroGenics
• Original Responsible Party: Same as current
• Current Study Sponsor: MacroGenics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ashley L. Ward, MD; MacroGenics

• PRS Account: MacroGenics
• Verification Date: May 2022