Clinical trial NCT06062420: A 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- GALAXIES H&N-202
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neoplasms, Head and Neck
Keywords: Dostarlimab
Belrestotug
Nelistotug
GSK4381562
PD-L1
HNSCC
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: iTeos Therapeutics
First posted: 2023-10-02
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: Inclusion Criteria:

* Have histologically or cytologically-confirmed HNSCC that is R/M and 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. A fresh tumor tissue sample obtained within 90 days of screening is highly preferred, If fresh biopsy is not possible, an archival tumor specimen is acceptable unless it was obtained prior to administration of chemoradiation for the treatment of a participant's tumour. 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.)

Primary outcomes:
measure: Confirmed Objective Response Rate (ORR) compared between Sub studies and Dostarlimab monotherapy
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Overall Survival (OS) compared between Sub studies and Dostarlimab monotherapy
timeFrame: Up to approximately 24 months
measure: Duration of Response (DOR) compared between Sub studies and Dostarlimab monotherapy
timeFrame: Up to approximately 24 months
measure: Progression Free Survival (PFS) compared between Sub studies and Dostarlimab monotherapy
timeFrame: Up to approximately 24 months
measure: Confirmed ORR by BICR compared between Sub studies and Dostarlimab monotherapy
timeFrame: Up to approximately 24 months
measure: Rate of Circulating Tumor Deoxyribonucleic Acid (ctDNA) Molecular Response
timeFrame: Up to approximately 24 months
measure: Confirmed Objective Response Rate (ORR) compared between Sub study 3 and Sub studies 1 and 2
timeFrame: Up to approximately 24 months
measure: Overall Survival (OS) compared between Sub study 3 and Sub studies 1 and 2
timeFrame: Up to approximately 24 months
measure: Progression Free Survival (PFS) compared between Sub study 3 and Sub studies 1 and 2
timeFrame: Up to approximately 24 months
measure: Confirmed ORR by BICR compared between sub study 3 and Sub studies 1 and 2
timeFrame: Up to approximately 24 months
measure: Rate of ctDNA Molecular Response compared between sub study 3 and Sub studies 1 and 2
timeFrame: Up to approximately 24 months
measure: Number of Participants with Treatment Emergent Adverse Events (AEs), treatment emergent Serious Adverse Events (SAE) and treatment emergent Adverse Events of Special Interest (AESI)
timeFrame: Up to approximately 24 months
measure: Number of Participants with TEAEs leading to dose modifications or study intervention discontinuation
timeFrame: Up to approximately 24 months
measure: Number of Participants with Clinically Significant Findings in Vital signs, Electrocardiogram (ECG), and Laboratory test parameters
timeFrame: Up to approximately 24 months
measure: Number of Participants with Anti-Drug Antibodies (ADA) against Dostarlimab
timeFrame: Up to approximately 24 months
measure: Number of Participants with Anti-Drug Antibodies (ADA) against Belrestotug
timeFrame: Up to approximately 24 months
measure: Number of Participants with Anti-Drug Antibodies (ADA) against nelistotug
timeFrame: Up to approximately 24 months
measure: Number of Participants with Anti-Drug Antibodies (ADA) against GSK4381562
timeFrame: Up to approximately 24 months
measure: Maximum Concentration (Cmax) and Minimum Concentration (Cmin) of Dostarlimab
timeFrame: Up to approximately 24 months
measure: Cmax and Cmin of Belrestotug
timeFrame: Up to approximately 24 months
measure: Cmax and Cmin of nelistotug
timeFrame: Up to approximately 24 months
measure: Cmax and Cmin of GSK4381562
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: New Haven
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Columbus
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Iowa City
country: United States
facility: GSK Investigational Site
state: Iowa
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Milwaukee
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Capital Federal
country: Argentina
facility: GSK Investigational Site
city: Capital Federal
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma De Bueno
country: Argentina
facility: GSK Investigational Site
city: Cordoba
country: Argentina
facility: GSK Investigational Site
city: Florida
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: San Juan
country: Argentina
facility: GSK Investigational Site
city: Santa Fe
country: Argentina
facility: GSK Investigational Site
city: Santo Andre
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Herlev
country: Denmark
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Bordeaux
country: France
facility: GSK Investigational Site
city: Caen Cedex 5
country: France
facility: GSK Investigational Site
city: Marseille cedex 5
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Rouen Cedex 1
country: France
facility: GSK Investigational Site
city: Villejuif Cedex
country: France
facility: GSK Investigational Site
city: Aachen
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Essen
country: Germany
facility: GSK Investigational Site
city: Frankfurt
country: Germany
facility: GSK Investigational Site
city: Giessen
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Leipzig
country: Germany
facility: GSK Investigational Site
city: Regensburg
country: Germany
facility: GSK Investigational Site
city: Ulm
country: Germany
facility: GSK Investigational Site
city: Haidari - Athens
country: Greece
facility: GSK Investigational Site
city: Marousi
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Gyor
country: Hungary
facility: GSK Investigational Site
city: KecskemEt
country: Hungary
facility: GSK Investigational Site
city: Nyiregyhaza
country: Hungary
facility: GSK Investigational Site
city: PEcs
country: Hungary
facility: GSK Investigational Site
city: Bari
country: Italy
facility: GSK Investigational Site
city: Bologna
country: Italy
facility: GSK Investigational Site
city: Firenze
country: Italy
facility: GSK Investigational Site
city: Genova
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
city: Novara
country: Italy
facility: GSK Investigational Site
city: Padova
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Rozzano MI
country: Italy
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Daegu
country: Korea, Republic of
facility: GSK Investigational Site
city: Seongnam-si Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon Kyunggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Oslo
country: Norway
facility: GSK Investigational Site
city: Bielsko-Biala
country: Poland
facility: GSK Investigational Site
city: Gliwice
country: Poland
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Koszalin
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Przemysl
country: Poland
facility: GSK Investigational Site
city: Siedlce
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Almada
country: Portugal
facility: GSK Investigational Site
city: Lisboa
country: Portugal
facility: GSK Investigational Site
city: Porto
country: Portugal
facility: GSK Investigational Site
city: Porto
country: Portugal
facility: GSK Investigational Site
city: Brasov
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Craiova
country: Romania
facility: GSK Investigational Site
city: Craiova
country: Romania
facility: GSK Investigational Site
city: Floresti
country: Romania
facility: GSK Investigational Site
city: Iasi
country: Romania
facility: GSK Investigational Site
city: Oradea
country: Romania
facility: GSK Investigational Site
city: Pitesti
country: Romania
facility: GSK Investigational Site
city: Suceava
country: Romania
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: JaEn
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Pozuelo De AlarcOn Madr
country: Spain
facility: GSK Investigational Site
city: Salamanca
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Zaragoza
country: Spain
facility: GSK Investigational Site
city: Changhua
country: Taiwan
facility: GSK Investigational Site
city: Tainan
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Ankara
country: Turkey
facility: GSK Investigational Site
city: Antalya
country: Turkey
facility: GSK Investigational Site
city: Istanbul
country: Turkey
facility: GSK Investigational Site
city: Izmir
country: Turkey
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: