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A Study of Dostarlimab vs Placebo After Chemoradiation in Adult Participants With Locally Advanced Unresected Head and Neck Squamous Cell Carcinoma

Phase 3
Recruiting
Conditions
Neoplasms, Head and Neck
Interventions
Drug: Placebo
Registration Number
NCT06256588
Lead Sponsor
GlaxoSmithKline
Brief Summary

The goal of this study is to assess the safety and effectiveness of Dostarlimab compared to Placebo in adult participants with HNSCC (Head and Neck Squamous Cell Carcinoma)

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
864
Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

  • Has newly diagnosed unresected LA histologically confirmed HNSCC of the oral cavity, oropharynx, hypopharynx or larynx and completed cisplatin plus radiotherapy (termed "CRT" in this protocol) with curative intent and has no evidence of distant metastatic disease.

  • Has provided acceptable core or excisional tissue demonstrating:

    • PD-L1 positive tumor status
    • If the primary tumor site is oropharyngeal carcinoma, the participant must have p16 IHC testing.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

  • Has adequate organ function.

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

  • Has received prior radiation therapy, systemic therapy, targeted therapy, or radical surgery for management of head and neck cancer not considered part of CRT.
  • Has cancer outside of the oropharynx, larynx, hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer.
  • Has experienced any of the following with prior immunotherapy: any irAE of Grade ≥3, immune-related severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade [Stevens-Johnson Syndrome, toxic epidermal necrolysis, or DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome], or myocarditis of any grade. Non-clinically significant laboratory abnormalities are not exclusionary.
  • Has undergone any major surgical procedure or experienced significant traumatic injury within 28 days prior to enrolment.
  • Has any history of interstitial lung disease or pneumonitis (past or current).
  • Has cirrhosis or current unstable liver biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.
  • Has a history or current evidence of any medical condition, therapy, or laboratory abnormality that might confound the study results, interfere with their participation for the full duration of the study intervention, or indicate it is not in the best interest of the participant to participate, in the opinion of the investigator.
  • Is receiving any other anticancer or experimental therapy. No other experimental therapies (including but not limited to chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, or other experimental drugs) of any kind are permitted while the participant is receiving study intervention.
  • Previous treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or an agent directed to another stimulatory or coinhibitory T-cell receptor [e.g., Cytotoxic T-lymphocyte associated protein 4 (CTLA4), OX-40, CD137]
  • Is pregnant, breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the Screening Visit through 120 days after the last dose of study intervention.
  • Has a history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies, fusion proteins, or known allergies to dostarlimab or its excipients.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm A: DostarlimabDostarlimab-
Arm B: PlaceboPlacebo-
Primary Outcome Measures
NameTimeMethod
Event-free Survival (EFS) Assessed by Blinded Independent Central Review (BICR)Up to approximately 5 years

Event Free Survival (EFS) is defined as the time from the date of randomization to the date of an event, where an event is defined as locoregional progression or recurrence, or distant metastasis per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as per BICR; Salvage surgery at the primary tumor site; Neck dissection or surgery performed \>20 weeks after completion of or Death from any cause.

Secondary Outcome Measures
NameTimeMethod
Number of Participants with treatment emergent adverse events (TEAEs), Immune-mediated TEAEs, and serious adverse events (SAEs) by severityUp to approximately 5 years
Number of Participants with Anti-Drug Antibodies against DostarlimabUp to approximately 15 months
Overall Survival (OS)Up to approximately 5 years

OS is defined as the time from date of randomization to the date of death by any cause.

Event-free Survival (EFS) assessed by investigatorUp to approximately 5 years

Event Free Survival (EFS) is defined as the time from the date of randomization to the date of an event as per primary endpoint, however with investigator assessment per RECIST 1.1

Number of participants with clinically significant changes in laboratory, vital signs, and safety assessment parametersUp to approximately 5 years
Serum Concentration of DostarlimabUp to approximately 15 months
Serum Concentration of Dostarlimab at End of Infusion (C-EoI)Up to approximately 15 months
Number of Participants with TEAEs and SAEs leading to dose delays, withdrawals or deathUp to approximately 5 years
Serum Predose trough concentration (Ctrough) of DostarlimabUp to approximately 15 months

Trial Locations

Locations (1)

GSK Investigational Site

🇬🇧

Wolverhampton, United Kingdom

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