Neoplasms, Head and Neck
Conditions
Keywords
Dostarlimab, Belrestotug, Nelistotug, Remzistotug, PD-L1, HNSCC
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).
Interventions
DRUGDostarlimab
Dostarlimab will be administered.
DRUGBelrestotug
Belrestotug will be administered.
DRUGNelistotug
Nelistotug will be administered.
DRUGRemzistotug
Remzistotug will be administered.
Sponsors
iTeos Therapeutics
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 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
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Objective Response Rate (ORR) compared between Sub studies and Dostarlimab monotherapy | Up to approximately 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Circulating Tumor Deoxyribonucleic Acid (ctDNA) Molecular Response | Up to approximately 24 months | 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. |
| Number of Participants with Treatment Emergent Adverse Events (AEs), treatment emergent Serious Adverse Events (SAE) and treatment emergent Adverse Events of Special Interest (AESI) | Up to approximately 24 months | — |
| Number of Participants with TEAEs leading to dose modifications or study intervention discontinuation | Up to approximately 24 months | — |
| Number of Participants with Clinically Significant Findings in Vital signs, Electrocardiogram (ECG), and Laboratory test parameters | Up to approximately 24 months | — |
Countries
Argentina, Brazil, Canada, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Norway, Poland, Portugal, Romania, South Korea, Spain, Taiwan, Turkey (Türkiye), United States
Outcome results
None listed