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).

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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 tumor. 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

Criterios de exclusión

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.)

Ubicaciones

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Capital Federal, Argentina

GSK Investigational Site

Ciudad Autonoma de Bueno, Argentina

GSK Investigational Site

Córdoba, Argentina

GSK Investigational Site

Florida, Argentina

GSK Investigational Site

Mendoza, Argentina

GSK Investigational Site

San Juan, Argentina

GSK Investigational Site

Santa Fe, Argentina

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

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Dostarlimab

Belrestotug

Nelistotug

Remzistotug

Ubicaciones

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

Patrocinadores