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

Phase 2

Recruiting

• Conditions: Neoplasms, Head and Neck
• Interventions: Drug: Dostarlimab; Drug: Belrestotug; Drug: GSK4381562; Drug: Nelistotug

• Registration Number: NCT06062420
• Lead Sponsor: GlaxoSmithKline

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-21
• Study First Submitted QC: 2023-09-29
• Study First Posted: 2023-10-02
• Study Start: 2023-11-14
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-28
• Last Update Posted: 2025-05-30
• Primary Completion: 2027-05-14
• Study Completion: 2027-05-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 360

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.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sub study 2: Dostarlimab and nelistotug	Dostarlimab	-
Sub study 3: Dosarlimab and Belrestotug and nelistotug	Belrestotug	-
Dostarlimab Monotherapy	Dostarlimab	-
Sub study 3: Dosarlimab and Belrestotug and nelistotug	Nelistotug	-
Sub study 1: Dostarlimab and Belrestotug	Belrestotug	-
Sub study 3: Dosarlimab and Belrestotug and nelistotug	Dostarlimab	-
Sub study 4: Dostarlimab and GSK4381562	Dostarlimab	-
Sub study 4: Dostarlimab and GSK4381562	GSK4381562	-
Sub study 1: Dostarlimab and Belrestotug	Dostarlimab	-
Sub study 2: Dostarlimab and nelistotug	Nelistotug	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Overall Survival (OS) compared between Sub studies and Dostarlimab monotherapy	Up to approximately 24 months	OS is defined as the time from the date of randomization to the date of death due to any cause.
Duration of Response (DOR) compared between Sub studies and Dostarlimab monotherapy	Up to approximately 24 months	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.
Progression Free Survival (PFS) compared between Sub studies and Dostarlimab monotherapy	Up to approximately 24 months	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.
Confirmed ORR by BICR compared between Sub studies and Dostarlimab monotherapy	Up to approximately 24 months	Confirmed ORR defined as the percentage of participants achieving confirmed CR or PR per RECIST 1.1 by Blinded Independent Central Review (BICR).
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
Confirmed Objective Response Rate (ORR) compared between Sub study 3 and Sub studies 1 and 2	Up to approximately 24 months	Confirmed ORR is defined as the percentage of participants achieving confirmed CR or PR per RECIST version 1.1 by investigator assessment.
Overall Survival (OS) compared between Sub study 3 and Sub studies 1 and 2	Up to approximately 24 months	OS is defined as the time from the date of randomization to the date of death due to any cause.
Progression Free Survival (PFS) compared between Sub study 3 and Sub studies 1 and 2	Up to approximately 24 months	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.
Confirmed ORR by BICR compared between sub study 3 and Sub studies 1 and 2	Up to approximately 24 months	Confirmed ORR defined as the percentage of participants achieving confirmed CR or PR per RECIST v1.1 by BICR.
Rate of ctDNA Molecular Response compared between sub study 3 and Sub studies 1 and 2	Up to approximately 24 months
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
Cmax and Cmin of nelistotug	Up to approximately 24 months
Cmax and Cmin of GSK4381562	Up to approximately 24 months
Number of Participants with Anti-Drug Antibodies (ADA) against Dostarlimab	Up to approximately 24 months
Number of Participants with Anti-Drug Antibodies (ADA) against Belrestotug	Up to approximately 24 months
Number of Participants with Anti-Drug Antibodies (ADA) against nelistotug	Up to approximately 24 months
Number of Participants with Anti-Drug Antibodies (ADA) against GSK4381562	Up to approximately 24 months
Maximum Concentration (Cmax) and Minimum Concentration (Cmin) of Dostarlimab	Up to approximately 24 months
Cmax and Cmin of Belrestotug	Up to approximately 24 months

Trial Locations

Locations (1)

GSK Investigational Site; 🇹🇷 Izmir, Turkey