Enoblituzumab Plus Retifanlimab or Tebotelimab in Head and Neck Cancer

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04634825
• Other study ID #: CP-MGA271-06
• Status: Terminated
• Phase: Phase 2
• Start date: March 17, 2021
• Est. completion date: July 29, 2022

Study information

• Verified date: December 2023
• Source: MacroGenics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 62
• Est. completion date: July 29, 2022
• Est. primary completion date: July 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Biological:
• Enoblituzumab
Anti-B7-H3 antibody
• Retifanlimab
Anti-PD-1 antibody
• Tebotelimab
PD-1 X LAG-3 bispecific DART molecule

Locations

Country	Name	City	State
Australia	Andrew Love Cancer Centre, Barwon Health	Geelong	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Monash Health, Medical Oncology Department	Ruse	New South Wales
Australia	Icon Cancer Centre Southport	Southport	Queensland
Australia	Royal North Shore Hospital	Sydney	New South Wales
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Bulgaria	Complex Oncology Center Ruse Ltd.	Dobrich
Bulgaria	MHAT Serdica	Panagyurishte
Bulgaria	MBAL Uni Hospital	Pleven
Bulgaria	COC Dobrich	Sofia
Bulgaria	MHAT Nadezhda, Medical Oncology	Sofia
Bulgaria	UMHAT Georgi Stranski Medical Oncology Department	Sofia
Bulgaria	UMHAT Tsarisa Yoanna - ISUL	Sofia
Hungary	Bajcsy-Zsilinszky Korhaz	Budapest
Hungary	Uzsoki Street Hospital	Budapest
Hungary	Dept of Oncology, University of Debrecen	Debrecen
Hungary	Dept of Oncology, Bekec County Hosp	Gyula
Hungary	Dept of Oncology, Tolna County Hospital	Szekszard
Poland	The Ewa Pilecka Department of Clinical Oncology	Bialystok
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	I Clinics of Radiotherapy and Chemiotherapy; The Maria Sklodowska-Curie National Research Institute of Oncology	Gliwice
Poland	Biokinetica	Jozefow
Poland	Clinics of Head and Neck Cancer, The Maria Sklodowska-Curie National Research Institute of Oncology	Warszawa
Spain	Complejo Hospitalario Universitario de Badajoz	Badajoz
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Universitario Vall D'Hebrón	Barcelona
Spain	Hospital Clínico San Carlos	Madrid
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Hospital Universitario Virgen de la Macarena	Sevilla
Ukraine	Communal Non-profit Enterprise "City Clinical Hospital#4" of Dnipro City	Dnipro
Ukraine	Communal Non-Profit Enterprise "Regional Center of Oncology", Oncosurgical Department of Head and Neck	Kharkiv
Ukraine	Communal Non-profit Enterprise "Regional Clinical Oncology Center of Kirovohrad Regional Council",	Kropyvnytskyi
Ukraine	Kyiv City Clinical Oncological Centre	Kyiv
Ukraine	Municipal Non-Profit Enterprise of Sumy Regional Council "Sumy Regional Clinical Oncology Dispensary"	Sumy
Ukraine	Communal Nonprofit Enterprise Podilsky Regional Center of Oncology	Vinnytsia
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Maryland, Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	University of North Carolina - Lineberger Cancer Center	Chapel Hill	North Carolina
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	University of Pennsylvania - Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center- Hillman Cancer Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Hungary,  Poland,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months.
Primary	Number of Patients With Adverse Events (AEs) Receiving Enoblituzumab Plus Tebotelimab		Throughout the study, up to 16.5 months.
Primary	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	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months
Secondary	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	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months
Secondary	Disease-control Rate (DCR)	Percentage of response-evaluable patients with CR, PR, or stable disease (SD) for at least 3 months, evaluated by cohort	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months
Secondary	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	Tumor assessment is conducted 6 weeks after the first dose, then every 9 weeks until disease progression, up to 16.5 months
Secondary	Overall Survival	Time from the first dose date to the date of death from any cause, evaluated by cohort	up to 16.5 months
Secondary	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	Tumor assessment is conducted 6 weeks after first dose, then every 9 weeks until disease progression, up to 16.5 months
Secondary	Number of Patients With AEs Receiving Enoblituzumab Plus Retifanlimab		Throughout the study, up to 16.5 months.
Secondary	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.	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)
Secondary	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.	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)
Secondary	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.	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)
Secondary	Trough Concentration of Enoblituzumab (Ctrough or Cmin)	The amount of enoblituzumab left in the bloodstream before the next dose is given.	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
Secondary	Trough Concentration of Tebotelimab (Ctrough or Cmin)	The amount of tebotelimab left in the bloodstream before the next dose is given.	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)
Secondary	Trough Concentration of Retifanlimab (Ctrough or Cmin)	The amount of retifanlimab left in the bloodstream before the next dose is given.	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)
Secondary	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
Secondary	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
Secondary	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