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

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Locally Advanced Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: volrustomig


Participation Criteria
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Eligibility Criteria
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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: Residual disease that needs further treatment with curative intent after definitive cCRT administration; LA-HNSCC that was resected before definitive cCRT 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Arm<br>Participants in this arm will receive volrustomig. | Drug: volrustomig<br>* volrustomig<br>* Other names: MEDI5752;|
| No Intervention: Observation Arm<br>Patients in this arm will undergo observation. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Presence of Anti-Drug-Antibodies (ADAs) against volrustomig in serum | To investigate the immunogenicity of volrustomig. | Up to approximately 7 years | 
| 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 | 
| 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 | 
| Percentage of participants with Adverse Events | Adverse Events as assessed by Common Terminology Criteria for Adverse Events (CTCAE). | Up to approximately 7 years | 
| 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 | 
| 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 | 
| 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 |