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

Phase 3

Recruiting

• Conditions: Locally Advanced Head and Neck Squamous Cell Carcinoma
• Interventions: Drug: volrustomig

• Registration Number: NCT06129864
• Lead Sponsor: AstraZeneca

Brief 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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-11-03
• Study First Submitted QC: 2023-11-10
• Study First Posted: 2023-11-13
• Study Start: 2023-12-14
• Status Verified: 2024-09
• Last Update Submitted: 2024-10-02
• Last Update Posted: 2024-10-03
• Primary Completion: 2029-01-19
• Study Completion: 2030-05-23

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1145

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study Arm	volrustomig	Participants in this arm will receive volrustomig.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) in participants with unresected LA-HNSCC with PD-L1 expressing tumors	Up to approximately 7 years	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.

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) in the unresected LA-HNSCC intent-to-treat (ITT) population	Up to approximately 7 years	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.
Overall Survival (OS) in participants with unresected LA-HNSCC with PD-L1 expressing tumors	Up to approximately 7 years	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.
Overall Survival (OS) in the unresected LA-HNSCC ITT population	Up to approximately 7 years	OS is defined as the time from randomization until the date of death due to any cause.; The analysis will include all randomized participants.
Progression Free Survival 2 (PFS2)	Up to approximately 7 years	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.
The time taken to reach the maximum concentration (Tmax)	Up to approximately 7 years	The concentration of MEDI5752 in serum will be determined (Tmax will be derived).
Participant-reported physical functioning	Up to approximately 7 years	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.
Landmark Progression-Free Survival (PFS) Rates	Up to approximately 7 years	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.
Landmark Overall Survival (OS) Rates	Up to approximately 7 years	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.
Presence of Anti-Drug-Antibodies (ADAs) against volrustomig in serum	Up to approximately 7 years	To investigate the immunogenicity of volrustomig.
Participant-reported global health status (GHS)/quality of life (QoL)	Up to approximately 7 years	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.
Area under the curve (AUC)	Up to approximately 7 years	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.
Maximum plasma concentration of the drug (Cmax)	Up to approximately 7 years	The concentration of MEDI5752 in serum will be determined (Cmax will be derived).
Percentage of participants with Adverse Events	Up to approximately 7 years	Adverse Events as assessed by Common Terminology Criteria for Adverse Events (CTCAE).

Trial Locations

Locations (1)

Research Site; 🇻🇳 Vinh, Vietnam