A Global Study of Volrustomig (MEDI5752) for Participants With Unresected Locally Advanced Head and Neck Squamous Cell Carcinoma Following Definitive Concurrent Chemoradiotherapy

Locally Advanced Head and Neck Squamous Cell Carcinoma Clinical Trial

— eVOLVE-HNSCC  

Official title:

A Phase III, Randomized, Open-Label, Multi-Center, Global Study of Volrustomig (MEDI5752) as Sequential Therapy Versus Observation in Participants With Unresected Locally Advanced Head and Neck Squamous Cell Carcinoma, Who Have Not Progressed Following Definitive Concurrent Chemoradiotherapy (eVOLVE-HNSCC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06129864
• Other study ID #: D798EC00001
• Status: Recruiting
• Phase: Phase 3
• Start date: December 14, 2023
• Est. completion date: June 17, 2030

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to assess the efficacy and safety of volrustomig compared to observation in participants with unresected locally advanced head and neck squamous cell carcinoma (LA-HNSCC) who have not progressed after receiving definitive concurrent chemoradiotherapy (cCRT).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1145
• Est. completion date: June 17, 2030
• Est. primary completion date: January 19, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

• Histologically or cytologically documented locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, oral cavity, or larynx with no evidence of metastatic disease (i.e. M0).

• Confirmed unresected Stage III, Stage IVA or IVB according to the eighth edition of the American Joint Committee on Cancer (AJCC) staging manual (tumor, node, metastasis (TNM) staging system).

• Participants will have completed definitive concurrent chemoradiotherapy (cCRT) with curative intent within 12 weeks prior to randomization.

Exclusion Criteria:

• Histologically/cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including participants with squamous cell carcinoma of unknown primary or non-squamous histologies (eg, nasopharynx or salivary gland). Participants with >1 primary tumors are not eligible for the study.

• Participants with any of the following:

1. Residual disease that needs further treatment with curative intent after definitive cCRT administration;

2. LA-HNSCC that was resected before definitive cCRT

3. LA-HNSCC that was treated and is recurrent at the time of screening

• Participants who have received radiotherapy (RT) alone as definitive local therapy for LA-HNSCC.

• Receipt of the last dose of anticancer therapy (chemotherapy and/or RT) > 12 weeks (84 days) prior to randomization.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Locally Advanced Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• volrustomig
volrustomig

Locations

Country	Name	City	State
Austria	Research Site	Innsbruck
Austria	Research Site	Linz
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Belgium	Research Site	Charleroi
Belgium	Research Site	Edegem
Belgium	Research Site	Jette
Brazil	Research Site	Barretos
Brazil	Research Site	Florianópolis
Brazil	Research Site	Fortaleza
Brazil	Research Site	Ijuí
Brazil	Research Site	Ipatinga
Brazil	Research Site	Londrina
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Ribeirão Preto
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Teresina
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Kelowna	British Columbia
Canada	Research Site	Kingston	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
France	Research Site	Avignon Cedex 09
France	Research Site	Bordeaux
France	Research Site	Lyon
France	Research Site	Saint Herblain
France	Research Site	Toulouse Cedex 09
France	Research Site	Villejuif
Germany	Research Site	Berlin
Germany	Research Site	Essen
Germany	Research Site	Greifswald
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Lübeck
Germany	Research Site	München
Germany	Research Site	Rostock
Germany	Research Site	Tübingen
Germany	Research Site	Ulm
Germany	Research Site	Würzburg
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Gyor
Hungary	Research Site	Kecskemét
Hungary	Research Site	Miskolc
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Pécs
Hungary	Research Site	Szekszárd
India	Research Site	Bengaluru
India	Research Site	Hyderabad
India	Research Site	Jaipur
India	Research Site	Kochi
India	Research Site	Kolkata
India	Research Site	Lucknow
India	Research Site	Madurai
India	Research Site	Mohali
India	Research Site	New Delhi
India	Research Site	Thiruvananthapuram
India	Research Site	Vadodara
India	Research Site	Varanasi
Italy	Research Site	Aviano
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Modena
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Pavia
Italy	Research Site	Rozzano
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chiba-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Kashiwa
Japan	Research Site	Kobe-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shiwa-gun
Japan	Research Site	Sunto-gun
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Gyeonggi-do
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Malaysia	Research Site	George Town
Malaysia	Research Site	Johor Bahru
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuching
Malaysia	Research Site	Selangor
Poland	Research Site	Bialystok
Poland	Research Site	Bielsko-Biala
Poland	Research Site	Gliwice
Poland	Research Site	Piotrków Trybunalski
Poland	Research Site	Tomaszów Mazowiecki
Poland	Research Site	Warszawa
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Jaén
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Valencia
Spain	Research Site	Valencia
Taiwan	Research Site	Changhua
Taiwan	Research Site	Kaohsiung City
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Chaing Mai
Thailand	Research Site	Hat Yai
Thailand	Research Site	Khon Kaen
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Antalya
Turkey	Research Site	Istanbul
Turkey	Research Site	Karsiyaka
Turkey	Research Site	Yenimahalle
United Kingdom	Research Site	Aberdeen
United Kingdom	Research Site	Hampshire
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Northwood
United Kingdom	Research Site	Sutton
United Kingdom	Research Site	Taunton
United Kingdom	Research Site	Wirral
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Aurora	Colorado
United States	Research Site	Austin	Texas
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boston	Massachusetts
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cleveland	Ohio
United States	Research Site	Columbia	Missouri
United States	Research Site	Columbia	Maryland
United States	Research Site	Dallas	Texas
United States	Research Site	Des Moines	Iowa
United States	Research Site	East Brunswick	New Jersey
United States	Research Site	Fairfax	Virginia
United States	Research Site	Flower Mound	Texas
United States	Research Site	Gainesville	Florida
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Houston	Texas
United States	Research Site	Hyattsville	Maryland
United States	Research Site	Kansas City	Kansas
United States	Research Site	Lone Tree	Colorado
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Miami	Florida
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Brunswick	New Jersey
United States	Research Site	New York	New York
United States	Research Site	Niles	Illinois
United States	Research Site	Norfolk	Virginia
United States	Research Site	Odessa	Texas
United States	Research Site	Orange	California
United States	Research Site	Palm Bay	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Portland	Oregon
United States	Research Site	Prescott Valley	Arizona
United States	Research Site	Richmond	Virginia
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Francisco	California
United States	Research Site	Santa Rosa	California
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Spokane	Washington
United States	Research Site	Springdale	Arkansas
United States	Research Site	Stony Brook	New York
United States	Research Site	Tacoma	Washington
United States	Research Site	Tacoma	Washington
United States	Research Site	Towson	Maryland
United States	Research Site	Tyler	Texas
United States	Research Site	West Jordan	Utah
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	York	Pennsylvania
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh City
Vietnam	Research Site	Vinh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Austria,  Belgium,  Brazil,  Canada,  France,  Germany,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Poland,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) in participants with unresected LA-HNSCC with PD-L1 expressing tumors	PFS is defined as time from randomization until first objective radiological progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause (in the absence of progression).; The analysis will include all randomized participants with PD-L1 expressing tumors.	Up to approximately 7 years
Secondary	Progression-Free Survival (PFS) in the unresected LA-HNSCC intent-to-treat (ITT) population	PFS is defined as time from randomization until first objective radiological progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression).; The analysis will include all randomized participants.	Up to approximately 7 years
Secondary	Landmark Progression-Free Survival (PFS) Rates	PFS is defined as time from randomization until first objective radiological progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression).; These analyses will include participants with PD-L1 expressing tumors and all randomized participants.	Up to approximately 7 years
Secondary	Overall Survival (OS) in participants with unresected LA-HNSCC with PD-L1 expressing tumors	Overall survival (OS) is defined as the time from randomization until the date of death due to any cause.; The analysis will include all randomized participants with PD-L1 expressing tumors.	Up to approximately 7 years
Secondary	Landmark Overall Survival (OS) Rates	OS is defined as the time from randomization until the date of death due to any cause.; These analyses will include participants with PD-L1 expressing tumors as randomized and all randomized participants.	Up to approximately 7 years
Secondary	Overall Survival (OS) in the unresected LA-HNSCC ITT population	OS is defined as the time from randomization until the date of death due to any cause.; The analysis will include all randomized participants.	Up to approximately 7 years
Secondary	Progression Free Survival 2 (PFS2)	PFS2 is defined as the time from randomization until the earliest of the progression event (following the initial investigator-assessed progression), after the start of the first subsequent therapy, or death from any cause, whichever occurs first. The date of the second progression will be recorded by the investigator in the eCRF and defined according to local standard clinical practice.; These analyses will include participants with PD-L1 expressing tumors as randomized and all randomized participants.	Up to approximately 7 years
Secondary	Presence of Anti-Drug-Antibodies (ADAs) against volrustomig in serum	To investigate the immunogenicity of volrustomig.	Up to approximately 7 years
Secondary	Participant-reported physical functioning	Change from baseline of physical functioning as measured by scores on the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v.20 - Physical Function 8c are reported on a T score metric (mean = 50 and SD = 10), with higher scores reflecting better physical functioning.; The analysis will include all randomized participants.	Up to approximately 7 years
Secondary	Participant-reported global health status (GHS)/quality of life (QoL)	Change from baseline of Global Health Status/Quality of Life subscale scores as measured by the European Organization for Research and Treatment of Cancer (EORTC) Item Library 172 are transformed to a 0-100 range; a higher score represents higher quality of life.; The analysis will include all randomized participants.	Up to approximately 7 years
Secondary	Percentage of participants with Adverse Events	Adverse Events as assessed by Common Terminology Criteria for Adverse Events (CTCAE).	Up to approximately 7 years
Secondary	Area under the curve (AUC)	The concentration of MEDI5752 in serum will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.	Up to approximately 7 years
Secondary	Maximum plasma concentration of the drug (Cmax)	The concentration of MEDI5752 in serum will be determined (Cmax will be derived).	Up to approximately 7 years
Secondary	The time taken to reach the maximum concentration (Tmax)	The concentration of MEDI5752 in serum will be determined (Tmax will be derived).	Up to approximately 7 years