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

GlaxoSmithKline (GSK)

Status and phase: Active, not recruiting; Phase 2

Conditions: Neoplasms, Head and Neck

Treatments: Drug: Belrestotug; Drug: Nelistotug; Drug: Remzistotug; Drug: Dostarlimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06062420

2023-503428-24 (Other Identifier)

219885

Details and patient eligibility

About

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).

Enrollment: 316 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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316 participants in 5 patient groups

Dostarlimab Monotherapy

Experimental group

Treatment:

Drug: Dostarlimab

Sub study 1: Dostarlimab and Belrestotug

Experimental group

Treatment:

Drug: Dostarlimab

Drug: Belrestotug

Sub study 2: Dostarlimab and nelistotug

Experimental group

Treatment:

Drug: Dostarlimab

Drug: Nelistotug

Sub study 3: Dosarlimab and Belrestotug and nelistotug

Experimental group

Treatment:

Drug: Dostarlimab

Drug: Nelistotug

Drug: Belrestotug

Sub study 4: Dostarlimab and remzistotug

Experimental group

Treatment:

Drug: Dostarlimab

Drug: Remzistotug