Phase 2 Platform Study of Novel Immunotherapy Combinations as First-Line Treatment in Participants With PD-L1 Positive Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

Neoplasms, Head and Neck Clinical Trial

Official title:

A Phase 2, Randomized, Open-label, Platform Study Using a Master Protocol to Evaluate Novel Immunotherapy Combinations as First-Line Treatment in Participants With Recurrent/Metastatic PD-L1 Positive Squamous Cell Carcinoma of the Head and Neck

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06062420
• Other study ID #: 219885
• Secondary ID: 2023-503428-24-0
• Status: Recruiting
• Phase: Phase 2
• Start date: November 14, 2023
• Est. completion date: August 12, 2027

Study information

• Verified date: January 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of the study is to evaluate the antitumor activity and safety of novel immunotherapy combinations compared with dostarlimab in participants with Programmed death ligand 1 (PD-L1) positive Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: August 12, 2027
• Est. primary completion date: September 17, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have histologically or cytologically-confirmed R/M HNSCC that is considered incurable by local therapies. A) Subjects must not have had prior systemic therapy administered in the R/M setting. Chemoradiation therapy which was completed more than 4 months prior to signing consent if given as part of multimodal treatment for locally advanced disease is allowed B) The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx C) Subjects may not have a primary tumor site of nasopharynx (any histology)

• Has measurable (target) disease based on RECIST 1.1 as determined by the investigator.

• Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1

• Provides a tumor tissue sample obtained at the time of or after the initial diagnosis of R/M HNSCC. Although a fresh tumor tissue sample obtained within 90 days of screening is highly preferred, an archival tumor specimen (=2 years old) is acceptable. Biopsies obtained prior to the administration of any systemic therapy administered for the treatment of a participant's tumor (such as neoadjuvant/adjuvant therapy) are not acceptable. Needle or excisional biopsies or resected tissue is required. Cytological specimens such as fine needle aspirates, bone marrow samples, or cell blocks are not acceptable. Bone specimen is not acceptable.

• Has tumor Programmed death ligand 1 (PD-L1) expression

• If the primary tumor site is oropharyngeal carcinoma, the participant must have Human papillomavirus (HPV) results

Exclusion Criteria:

• Has received prior therapy with any immune checkpoint inhibitors, including antibodies or drugs targeting Programmed death protein 1 (PD-1), PD-L1, Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine based inhibitory motif domains (TIGIT), Cluster of differentiation (CD) 96, or other immune checkpoint pathways.

• Participants with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, esophageal, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.

• Have active tumor bleeding or a high risk of bleeding (examples include but are not limited to radiographic evidence of major blood vessel invasion/infiltration or tumor demonstrates >90 degree abutment or encasement of a major vessel [carotid, jugular, bronchial artery] and/or exhibits other high-risk features such as arteriovenous fistula).

• Has PD within 4 months of completion of curatively intended treatment for locoregionally advanced HNSCC

• Participants with any carcinomatous meningitis or leptomeningeal spread and those with uncontrolled or symptomatic Central Nervous System (CNS) metastases

• Active autoimmune disease that has required systemic disease-modifying or immunosuppressive treatment within the last 2 years. (Stable, medically managed autoimmune endocrinopathies are acceptable if participant otherwise meets entry criteria.)

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• Neoplasms, Head and Neck
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Dostarlimab
Dostarlimab will be administered.
• Belrestotug
Belrestotug will be administered.
• GSK6097608
GSK6097608 will be administered.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Capital Federal	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Cordoba
Argentina	GSK Investigational Site	Florida	Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	San Juan
Argentina	GSK Investigational Site	Santa Fe
Brazil	GSK Investigational Site	Santo Andre	Sao Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Canada	GSK Investigational Site	Calgary	Alberta
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Denmark	GSK Investigational Site	Herlev
Finland	GSK Investigational Site	Turku
France	GSK Investigational Site	Bordeaux Cedex
France	GSK Investigational Site	Caen Cedex 5
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Rouen
France	GSK Investigational Site	Saint Herblain
France	GSK Investigational Site	Villejuif Cedex
Germany	GSK Investigational Site	Aachen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Giessen	Hessen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Regensburg	Bayern
Germany	GSK Investigational Site	Ulm	Baden-Wuerttemberg
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Haidari, Athens
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
Hungary	GSK Investigational Site	Gyor
Hungary	GSK Investigational Site	Kecskemét
Hungary	GSK Investigational Site	Nyíregyháza
Hungary	GSK Investigational Site	Pécs
Hungary	GSK Investigational Site	Szolnok
Italy	GSK Investigational Site	Bari	Puglia
Italy	GSK Investigational Site	Bologna	Emilia-Romagna
Italy	GSK Investigational Site	Firenze	Toscana
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Napoli	Campania
Italy	GSK Investigational Site	Novara	Piemonte
Italy	GSK Investigational Site	Padova	Veneto
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Rozzano (MI)	Lombardia
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Saitama
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Daegu-si
Korea, Republic of	GSK Investigational Site	Seongnam-si, Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Norway	GSK Investigational Site	Oslo
Poland	GSK Investigational Site	Bielsko-Biala
Poland	GSK Investigational Site	Gliwice
Poland	GSK Investigational Site	Koszalin
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Przemysl
Poland	GSK Investigational Site	Siedlce
Poland	GSK Investigational Site	Warszawa
Portugal	GSK Investigational Site	Almada
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Porto
Portugal	GSK Investigational Site	Porto
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Craiova
Romania	GSK Investigational Site	Craiova
Romania	GSK Investigational Site	Floresti
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Oradea
Romania	GSK Investigational Site	Pitesti	Arges
Romania	GSK Investigational Site	Suceava
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Jaén
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Pozuelo De Alarcón/Madrid
Spain	GSK Investigational Site	Salamanca
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Zaragoza
Sweden	GSK Investigational Site	Stockholm
Taiwan	GSK Investigational Site	Changhua
Taiwan	GSK Investigational Site	Tainan
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei City
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Antalya
Turkey	GSK Investigational Site	Istanbul
Turkey	GSK Investigational Site	Izmir
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Iowa City	Iowa
United States	GSK Investigational Site	Milwaukee	Wisconsin
United States	GSK Investigational Site	New Haven	Connecticut
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	iTeos Therapeutics

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Italy,  Japan,  Korea, Republic of,  Norway,  Poland,  Portugal,  Romania,  Spain,  Sweden,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed Objective Response Rate (ORR) compared between Sub studies and Dostarlimab monotherapy	Confirmed ORR is defined as the percentage of participants achieving confirmed Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator assessment.	Up to approximately 24 months
Secondary	Overall Survival (OS) compared between Sub studies and Dostarlimab monotherapy	OS is defined as the time from the date of randomization to the date of death due to any cause.	Up to approximately 24 months
Secondary	Duration of Response (DOR) compared between Sub studies and Dostarlimab monotherapy	DOR per RECIST 1.1 by investigator assessment, defined as the time from the date of first documented objective response (CR or PR) to the date of first documented Disease progression (PD) or death due to any cause, whichever comes first.	Up to approximately 24 months
Secondary	Progression Free Survival (PFS) compared between Sub studies and Dostarlimab monotherapy	PFS per RECIST 1.1 by investigator assessment, defined as the time from the date of randomization to the date of first documented PD or death due to any cause, whichever comes first.	Up to approximately 24 months
Secondary	Disease Control Rate (DCR) compared between Sub studies and Dostarlimab monotherapy	DCR is defined as the percentage of participants achieving CR or PR, or Stable disease (SD) greater than or equal to (=) 6 months, per RECIST 1.1 by investigator assessment.	Up to approximately 24 months
Secondary	Rate of Circulating Tumor Deoxyribonucleic Acid (ctDNA) Molecular Response	The rate of ctDNA molecular response, is defined as the percentage of participants achieving a =50% decrease in ctDNA level compared to baseline, measured by plasma ctDNA assessment	Up to approximately 24 months
Secondary	Confirmed Objective Response Rate (ORR) compared between Sub study 3 and Sub studies 1 and 2	Confirmed ORR is defined as the percentage of participants achieving confirmed CR or PR per RECIST version 1.1 by investigator assessment.	Up to approximately 24 months
Secondary	Overall Survival (OS) compared between Sub study 3 and Sub studies 1 and 2	OS is defined as the time from the date of randomization to the date of death due to any cause.	Up to approximately 24 months
Secondary	Duration of Response (DOR) compared between Sub study 3 and Sub studies 1 and 2	DOR per RECIST v 1.1 by investigator assessment, defined as the time from the date of first documented objective response (CR or PR) to the date of first documented PD or death due to any cause, whichever comes first.	Up to approximately 24 months
Secondary	Progression Free Survival (PFS) compared between Sub study 3 and Sub studies 1 and 2	PFS per RECIST 1.1 by investigator assessment, defined as the time from the date of randomization to the date of first documented PD or death due to any cause, whichever comes first.	Up to approximately 24 months
Secondary	DCR compared between sub study 3 and Sub studies 1 and 2	DCR is defined as the percentage of participants achieving CR or PR, or Stable disease (SD) = 6 months, per RECIST v1.1 by investigator assessment.	Up to approximately 24 months
Secondary	Rate of ctDNA Molecular Response compared between sub study 3 and Sub studies 1 and 2		Up to approximately 24 months
Secondary	Number of Participants with Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAE) and Adverse Events of Special Interest (AESI)		Up to approximately 24 months
Secondary	Number of Participants with TEAEs or SAEs leading to dose modifications or study intervention discontinuation		Up to approximately 24 months
Secondary	Number of Participants with Clinically Significant Findings in Physical examination, Vital signs, Electrocardiogram (ECG), Echocardiogram (ECHO), Multigated acquisition (MUGA) and Laboratory test parameters		Up to approximately 24 months
Secondary	Number of Participants with Anti-Drug Antibodies (ADA) against Dostarlimab		Up to approximately 24 months
Secondary	Number of Participants with Anti-Drug Antibodies (ADA) against Belrestotug		Up to approximately 24 months
Secondary	Number of Participants with Anti-Drug Antibodies (ADA) against GSK6097608		Up to approximately 24 months
Secondary	Maximum Concentration (Cmax) and Minimum Concentration (Cmin) of Dostarlimab		Up to approximately 24 months
Secondary	Cmax and Cmin of Belrestotug		Up to approximately 24 months
Secondary	Cmax and Cmin of GSK6097608		Up to approximately 24 months