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Enoblituzumab Plus Retifanlimab or Tebotelimab in Head and Neck Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04634825
Recruitment Status : Terminated (Based on internal review of safety data)
First Posted : November 18, 2020
Last Update Posted : November 7, 2022
Sponsor:
Information provided by (Responsible Party):
MacroGenics

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.

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Head and Neck Neoplasms Head and Neck Squamous Cell Carcinoma Biological: Enoblituzumab Biological: Retifanlimab Biological: Tebotelimab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
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
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
Actual Study Start Date : March 17, 2021
Actual Primary Completion Date : July 29, 2022
Actual Study Completion Date : July 29, 2022

Resource links provided by the National Library of Medicine


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 Name: MGA271

Biological: Retifanlimab
Anti-PD-1 antibody
Other Name: INCMGA00012, MGA012

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 Name: MGA271

Biological: Tebotelimab
PD-1 X LAG-3 bispecific DART molecule
Other Name: MGD013




Primary Outcome Measures :
  1. Overall Response Rate (ORR) of enoblituzumab plus retifanlimab [ Time Frame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 28 months. ]
    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).

  2. Number of patients with AEs receiving enoblituzumab plus tebotelimab [ Time Frame: Throughout the study, up to 28 months. ]
    Incidence of treatment-emergent adverse events

  3. ORR of enoblituzumab plus tebotelimab [ Time Frame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 28 months ]
    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 :
  1. Progression-free survival [ Time Frame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 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

  2. Disease-control rate [ Time Frame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 28 months ]
    Percentage of response-evaluable patients with CR, PR, or stable disease (SD) for at least 3 months, evaluated by cohort

  3. Duration of response [ Time Frame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 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

  4. Overall survival [ Time Frame: up to 28 months ]
    Time from the first dose date to the date of death from any cause, evaluated by cohort

  5. Best overall response (BOR) [ Time Frame: Tumor assessment is conducted 6 weeks after first dose, then every 9 weeks until disease progression, up to 28 months ]
    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)

  6. Number of patients with AEs receiving enoblituzumab plus retifanlimab [ Time Frame: Throughout the study, up to 28 months. ]
    Incidence of treatment-emergent adverse events

  7. Maximum drug concentration or drug concentration of enoblituzumab at the end of infusion of enoblituzumab (Cmax) [ 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 ]
    The highest measured concentration of enoblituzumab in the bloodstream.

  8. Maximum drug concentration or drug concentration of tebotelimab at the end of infusion of tebotelimab (Cmax) [ 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 ]
    The highest measured concentration of tebotelimab in the bloodstream.

  9. Maximum drug concentration or drug concentration of retifanlimab at the end of infusion of enoblituzumab (Cmax) [ 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 ]
    The highest measured concentration of retifanlimab in the bloodstream.

  10. Trough concentration of enoblituzumab (Ctrough or Cmin) [ 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 ]
    The amount of tebotelimab left in the bloodstream before the next dose is given.

  11. Trough concentration of tebotelimab (Ctrough or Cmin) [ 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 ]
    The amount of tebotelimab left in the bloodstream before the next dose is given.

  12. Trough concentration of retifanlimab (Ctrough or Cmin) [ 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 ]
    The amount of retifanlimab left in the bloodstream before the next dose is given.

  13. 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 ]
  14. Number of patients who develop ADA to tebotelimab [ Time Frame: Prior to treatment and at the beginning of every 3-week cycle of treatment up to 28 months ]
    Proportion of patients who develop anti-drug antibodies to enoblituzumab or retifanlimab

  15. Number of patients who ADA to retifanlimab [ Time Frame: Prior to treatment and at the beginning of every 3-week cycle of treatment up to 28 months ]
    Proportion of patients who develop anti-drug antibodies to enoblituzumab or tebotelimab.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04634825


Locations
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Sponsors and Collaborators
MacroGenics
Investigators
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Study Director: Ashley L. Ward, MD MacroGenics
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Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT04634825    
Other Study ID Numbers: CP-MGA271-06
First Posted: November 18, 2020    Key Record Dates
Last Update Posted: November 7, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site