DOSTARLIMAB for Squamous cell carcinoma of head and neck

Inclusion criteria

• {"criterion_text":"- Is at least 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of signing the informed consent form (ICF).\n- 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.\n- 3. Disease defined as: a) Oropharyngeal p16 positive: T4 (N0-N3), M0; N3 (T1-T4), M0 b) Oropharyngeal p16 negative: Any T3-T4 (N0-N3), M0; Any N2a-N3 (T1-T4), M0 c) Larynx/hypopharynx/oral cavity (independent of p16): Any T3-T4 (N0-N3), M0; Any N2a-N3 (T1-T4), M0. NOTE: Tumors to be staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual (Amin, 2017). NOTE: Participants with distant metastases (defined as new tumor identified at a site distant from the head and neck anatomic region or draining lymph nodes), including central nervous system (CNS) metastases and/or carcinomatosis, are not eligible, either pre-CRT, or in the screening period post-CRT. NOTE: For eligibility assessment: TNM stage for oropharyngeal HNSCC must be based on p16 status as determined by CINtec assay.\n- 4. Participants must have met the following minimum requirements for CRT delivered as part of local SoC: a. For Cisplatin: Minimum cumulative exposure of 200 mg/m2 as part of CRT, delivered as either Q3W (e.g., 100 mg/m2 cycles), or Q1W (e.g., 40 mg/m2) cycles. Dose delays and dose modification are permitted per local practice providing all other requirements are met. It is recommended that concurrent cisplatin and RT be started and completed as close to each other as possible. b. Total Radiation dose of 65 Gy to 72 Gy over 6 – 7 weeks (up to +7 days if required) to the high-risk disease site.\n- 5. Has provided acceptable core or excisional biopsy obtained prior to CRT (see Laboratory Manual for detail) demonstrating: a. PD-L1 positive tumor status as defined by CPS ≥ 1 using the Agilent 22C3 assay performed at central laboratory. b. If the primary tumor site is oropharyngeal carcinoma, the participant must have HPV results defined as p16 IHC testing using the CINtec p16 histology assay and a ≥70% cutoff point (p16 IHC positive is ≥70% of carcinoma TC(s) with nuclear and cytoplasmic moderate to strong staining; see Section 8.1.5 for details). If HPV status was previously tested locally using the CINtec assay (compliant to applicable local regulation), no additional central lab testing will be required.\n- 6. Participants with known HIV infection are allowed with the following requirements: a) Documented evidence of plasma HIV-1 RNA levels persistently <50 c/mL confirmed ≤3 months prior to AND at screening; Plasma HIV-1 RNA consistently <50 c/ml required; if single increase >50 c/ml occurred, they cannot have been persistent nor associated with antiretroviral resistance per investigator assessment unless undetectable viral load is defined differently by local guidelines and agreed with the sponsor’s Central Study Team. In the 3 to 12 months prior to screening, plasma HIV-1 RNA levels consistently <50 c/mL are required; if single/isolated increases ≥50 c/mL occurred and are thought to be neither persistent nor associated with antiretroviral resistance per investigator assessment, the participant would be eligible if entry criteria are otherwise met. AND b) CD4 cell count ≥350 cells/mm3 over the 12 months prior to AND at screening (and no measurement <350cells/mm3 during that time period) AND c) Is on an uninterrupted combination antiretroviral therapy (ART) regimen for at least 3 months prior to screening, with a combination ART regimen consistent with locally recommended guidelines. NOTE: Participants who test as HIV positive during Screening will not be eligible for the study by default, owing to insufficient time to meet the safety requirements described in inclusion criteria 6, a, b, and c (above).\n- No history of HIV-associated non-Hodgkin lymphoma ≤5 years prior to study entry and no history of HIV- associated invasive cervical cancer.\n- No treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening."}

Exclusion criteria

• {"criterion_text":"- 1. Has received prior radiation therapy, systemic therapy, targeted therapy, or surgery for management of head and neck cancer not considered part of CRT. Participants receiving induction chemotherapy are excluded. CRT combinations with components other than cisplatin and RT (e.g., experimental agents, including radiosensitizers/radioprotectants, cetuximab) are not eligible.\n- 23. Has documented presence of HBsAg at Screening or within 3 months prior to randomization. Participants with a negative HBsAg and positive HBcAb result are eligible only if HBV DNA is negative.\n- 2. 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 more than one primary HNSCC tumor\n- Any unresolved toxicity CTCAE >Grade 2 from the prior CRT.\n- Has a known additional malignancy that progressed or required active treatment within the past 2 years.\n- Has Grade 3-4 bleeding due to underlying malignancy or has high risk of bleeding (examples include but not limited to tumors encasing or infiltrating a major vessel (i.e., carotid artery, jugular vein) and/or other high-risk features such as an arteriovenous fistula.\n- Is immunocompromised in the opinion of the investigator.\n- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.\n- 11. Has any history of interstitial lung disease or pneumonitis (past or current).\n- 8. Has experienced any of the following with prior immunotherapy: any imAE of Grade ≥3, immune-mediated 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 syndrome), or myocarditis of any grade. Non-clinically significant laboratory abnormalities are not exclusionary."}

Primary endpoints

• {"endpoint_text":"- Event Free Survival (EFS) where an event is defined as: • First record of locoregional progression or recurrence, or distant metastasis per RECIST 1.1 as per BICR, • Salvage surgery at the primary tumor site when invasive cancer is present, • Neck dissection or surgery performed >20 weeks after completion of CRT when invasive cancer is present, • Death from any cause.","definition_or_measurement_approach":"EFS defined by first record of locoregional progression or recurrence, or distant metastasis per RECIST 1.1 as per blinded independent central review (BICR); salvage surgery at primary site when invasive cancer is present; neck dissection/surgery >20 weeks after CRT when invasive cancer is present; or death from any cause."}

Secondary endpoints

• {"endpoint_text":"- OS, defined as time from randomization to death from any cause","definition_or_measurement_approach":"Overall survival measured as time from randomization to death from any cause."}
• {"endpoint_text":"- Event Free Survival (EFS) where an event is defined as: • First record of locoregional progression or recurrence, or distant metastasis per RECIST 1.1 as per investigator assessment. • Salvage surgery at the primary tumor site when invasive cancer is present. • Neck dissection or surgery performed >20 weeks after completion of CRT when invasive cancer is present. • Death from any cause.","definition_or_measurement_approach":"EFS as per investigator assessment using RECIST 1.1 criteria and surgical/end-point events as described."}
• {"endpoint_text":"- Frequency and severity of TEAEs, immune-mediated TEAEs, SAEs TEAE/SAEs leading to dose delays, withdrawal or death. Clinically significant changes in laboratory, vital signs, and safety assessment parameters","definition_or_measurement_approach":"Safety endpoints include incidence, frequency and severity (CTCAE) of TEAEs, immune-mediated TEAEs, SAEs, TEAE/SAEs leading to dose modifications, withdrawal or death; clinically significant laboratory, vital signs and other safety assessment changes."}
• {"endpoint_text":"- Serum concentrations and relevant PK parameters (C-EoI and C trough) for dostarlimab","definition_or_measurement_approach":"Pharmacokinetic assessments: serum concentrations and PK parameters including C at end of infusion (C-EoI) and trough concentration (C trough) for dostarlimab."}
• {"endpoint_text":"- Incidence of ADA against dostarlimab","definition_or_measurement_approach":"Immunogenicity assessed as incidence of anti-drug antibodies (ADA) against dostarlimab."}

Methods

• Use of study website (country-specific study websites) to provide trial information to potential participants
• Printed materials: trifold brochures and booklets (UYS book / UYS booklet / study trifold) for patients
• Video materials/storyboards (website video, storyboard for UIC/UCT) to explain trial and informed consent
• Healthcare professional outreach: GP/medical oncologist referral letters and study talking points provided to clinicians to facilitate referral
• Site-based recruitment via participating hospital/clinic sites
• Patient-facing materials in multiple languages and country-specific adaptations

Italy

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

02-02-2026

Number Of Participants

43

Czechia

Earliest CTIS Part Ii Submission Date

02-04-2024

Latest Decision Or Authorization Date

30-04-2026

Number Of Participants

21

Norway

Earliest CTIS Part Ii Submission Date

27-03-2024

Latest Decision Or Authorization Date

16-12-2025

Number Of Participants

12

Greece

Earliest CTIS Part Ii Submission Date

25-01-2024

Latest Decision Or Authorization Date

02-02-2026

Number Of Participants

25

Belgium

Earliest CTIS Part Ii Submission Date

03-04-2024

Latest Decision Or Authorization Date

02-02-2026

Number Of Participants

21

Hungary

Earliest CTIS Part Ii Submission Date

06-03-2024

Latest Decision Or Authorization Date

02-02-2026

Number Of Participants

12

Sweden

Earliest CTIS Part Ii Submission Date

27-03-2024

Latest Decision Or Authorization Date

30-01-2026

Number Of Participants

12

Poland

Earliest CTIS Part Ii Submission Date

02-04-2024

Latest Decision Or Authorization Date

03-02-2026

Number Of Participants

34

France

Earliest CTIS Part Ii Submission Date

25-01-2024

Latest Decision Or Authorization Date

12-03-2026

Number Of Participants

36

Portugal

Earliest CTIS Part Ii Submission Date

25-03-2024

Latest Decision Or Authorization Date

30-03-2026

Number Of Participants

40

Romania

Earliest CTIS Part Ii Submission Date

25-01-2024

Latest Decision Or Authorization Date

27-04-2026

Number Of Participants

44

Germany

Earliest CTIS Part Ii Submission Date

28-03-2024

Latest Decision Or Authorization Date

06-05-2026

Number Of Participants

21

Spain

Earliest CTIS Part Ii Submission Date

13-02-2024

Latest Decision Or Authorization Date

13-05-2026

Number Of Participants

43

Primary sponsor

Full Name

Glaxosmithkline Research & Development Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

IQVIA Limited

Responsibilities

ePROs collection; other CRO activities listed

Name

PPD Global Limited

Responsibilities

Operational duties including monitoring, data management and other sponsor duties (codes 1,5,8 listed)

Name

Sermes CRO

Responsibilities

Patient fee reimbursement

Third parties

• {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A.","duties_or_roles":"Sponsor duties codes present (code:4); local site and contact; listed as third party with contact","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom","full_name":"Veramed Limited","duties_or_roles":"Sponsor duties code 10","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"C & M Trial Support S.L.","duties_or_roles":"Management of biological samples","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Sponsor duties code 8; periodic reporting / MAPS","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Fm Richard Et Associes","duties_or_roles":"Reimbursement of patient fees / Payment of biological exams performed outside the sites","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"Companion Diagnostic development; sponsor duties code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Greece","full_name":"Idiotiko Diagnostiko Ergastirio Iatriki A.E.","duties_or_roles":"Sponsor duties code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Iqvia Rds Inc.","duties_or_roles":"ePROs collection","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Sermes CRO","duties_or_roles":"Patient fee reimbursement","organisation_type":"Pharmaceutical company / CRO"}
• {"country":"Germany","full_name":"ZALARIS Deutschland GmbH","duties_or_roles":"Patient fee reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Imaging collection and review, BICR","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Poland","full_name":"Komtur Polska Sp. z o.o.","duties_or_roles":"Ancillary study supplies provision","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"Medicine product destruction","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Theodoros Xionis","duties_or_roles":"Cardiovascular examination","organisation_type":"Health care"}
• {"country":"United States","full_name":"Jumo Health USA Inc.","duties_or_roles":"Recruitment material","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"IL-CSM Clinical Supplies Management GmbH","duties_or_roles":"Clinical supplies management (code 14)","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"Clinical supplies-related duties (code 14)","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Affidea Sp. z o.o.","duties_or_roles":"Imaging tests performing; PET and/or Bone scan","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom","full_name":"PPD Global Limited","duties_or_roles":"Multiple sponsor duties including code 1, 5, 8 (various operational responsibilities)","organisation_type":"Pharmaceutical company / CRO"}
• {"country":"Greece","full_name":"Raptis Lab","duties_or_roles":"Sponsor duties code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Italy","full_name":"Ospedale San Raffaele S.r.l.","duties_or_roles":"Sponsor duties code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Charles River Laboratories Inc.","duties_or_roles":"Sponsor duties code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"Sponsor duties code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Poland","full_name":"Komtur Polska Sp. z o.o.","duties_or_roles":"Ancillary study supplies provision","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Imaging collection and review, BICR","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Poland","full_name":"Let Me Pay Sp. z o.o.","duties_or_roles":"Patients' travel costs reimbursement management","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Italy","full_name":"Azienda Ospedaliero-Universitaria Sant Andre","duties_or_roles":"Sponsor duties code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Nespat Corp.","duties_or_roles":"Patient reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Poland","full_name":"Clinops Tomasz Lusawa","duties_or_roles":"Medical equipment rental","organisation_type":"Industry"}