Enoblituzumab Plus Retifanlimab or Tebotelimab in Head and Neck Cancer

Phase 2

Terminated

Conditions: Head and Neck Squamous Cell Carcinoma
Head and Neck Neoplasms
Head and Neck Cancer

Registration Number: NCT04634825

Lead Sponsor: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 62

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
ORR of Enoblituzumab Plus Tebotelimab	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months	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
Overall Response Rate (ORR) of Enoblituzumab Plus Retifanlimab	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months.	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
Number of Patients With Adverse Events (AEs) Receiving Enoblituzumab Plus Tebotelimab	Throughout the study, up to 16.5 months.

Secondary Outcome Measures

Name	Time	Method
Maximum Drug Concentration or Drug Concentration of Enoblituzumab at the End of Infusion of Enoblituzumab (Cmax)	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.
Maximum Drug Concentration or Drug Concentration of Tebotelimab at the End of Infusion of Tebotelimab (Cmax)	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.
Trough Concentration of Tebotelimab (Ctrough or Cmin)	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.
Trough Concentration of Retifanlimab (Ctrough or Cmin)	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.
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
Disease-control Rate (DCR)	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months	Percentage of response-evaluable patients with CR, PR, or stable disease (SD) for at least 3 months, evaluated by cohort
Overall Survival	up to 16.5 months	Time from the first dose date to the date of death from any cause, evaluated by cohort
Best Overall Response (BOR)	Tumor assessment is conducted 6 weeks after first dose, then every 9 weeks until disease progression, up to 16.5 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), 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
Maximum Drug Concentration or Drug Concentration of Retifanlimab at the End of Infusion of Enoblituzumab (Cmax)	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.
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
Progression-free Survival (PFS)	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 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
Duration of Response	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 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
Number of Patients With AEs Receiving Enoblituzumab Plus Retifanlimab	Throughout the study, up to 16.5 months.
Trough Concentration of Enoblituzumab (Ctrough or Cmin)	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 enoblituzumab left in the bloodstream before the next dose is given.

Trial Locations

Locations (42): University of Maryland, Greenebaum Comprehensive Cancer Center
🇺🇸
Baltimore, Maryland, United States
University of Michigan
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Ann Arbor, Michigan, United States
Comprehensive Cancer Centers of Nevada
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Las Vegas, Nevada, United States
University of North Carolina - Lineberger Cancer Center
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Chapel Hill, North Carolina, United States
University of Pennsylvania - Abramson Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center- Hillman Cancer Center
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Pittsburgh, Pennsylvania, United States
Liverpool Hospital
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Liverpool, New South Wales, Australia
Monash Health, Medical Oncology Department
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Ruse, New South Wales, Australia
Royal North Shore Hospital
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Sydney, New South Wales, Australia
Calvary Mater Newcastle
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Waratah, New South Wales, Australia
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University of Maryland, Greenebaum Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States