Enoblituzumab Plus Retifanlimab or Tebotelimab in Head and Neck Cancer

Phase 2TerminatedNCT04634825

MacroGenics62 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Interventions

EnoblituzumabBIOLOGICAL

Anti-B7-H3 antibody

RetifanlimabBIOLOGICAL

Anti-PD-1 antibody

TebotelimabBIOLOGICAL

PD-1 X LAG-3 bispecific DART molecule

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (42)

Outcomes

Primary Outcomes

Overall Response Rate (ORR) of Enoblituzumab Plus Retifanlimab

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

Time frame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months.

Number of Patients With Adverse Events (AEs) Receiving Enoblituzumab Plus Tebotelimab

Time frame: Throughout the study, up to 16.5 months.

ORR of Enoblituzumab Plus Tebotelimab

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

Time frame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months

Secondary Outcomes

Progression-free Survival (PFS)

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 16.5 months

Disease-control Rate (DCR)

Percentage of response-evaluable patients with CR, PR, or stable disease (SD) for at least 3 months, evaluated by cohort

Data from ClinicalTrials.gov

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University of Maryland, Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

University of North Carolina - Lineberger Cancer Center

Chapel Hill, North Carolina, United States

University of Pennsylvania - Abramson Cancer Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center- Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Liverpool Hospital

Liverpool, New South Wales, Australia

Monash Health, Medical Oncology Department

Ruse, New South Wales, Australia

Royal North Shore Hospital

Sydney, New South Wales, Australia

Calvary Mater Newcastle

Waratah, New South Wales, Australia

...and 32 more locations

Time frame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months

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

Time frame: Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months

Overall Survival

Time from the first dose date to the date of death from any cause, evaluated by cohort

Time frame: up to 16.5 months

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), 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

Time frame: Tumor assessment is conducted 6 weeks after first dose, then every 9 weeks until disease progression, up to 16.5 months

Number of Patients With AEs Receiving Enoblituzumab Plus Retifanlimab

Time frame: Throughout the study, up to 16.5 months.

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.

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)

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.

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)

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 enoblituzumab 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.

Time frame: 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 Develop ADA to Tebotelimab

Time frame: 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

Time frame: Prior to treatment (baseline) and at the beginning of every 3-week cycle of treatment (post baseline) up to 16.5 months