Clinical Trials/NCT06062420

NCT06062420

Active, Not Recruiting

Phase 2

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

GlaxoSmithKline112 sites in 11 countries316 target enrollmentNovember 14, 2023

ConditionsNeoplasms, Head and Neck

InterventionsRemzistotug Nelistotug Dostarlimab Belrestotug

DrugsDostarlimab Belrestotug Nelistotug

Overview

Phase: Phase 2
Intervention: Remzistotug
Conditions: Neoplasms, Head and Neck
Sponsor: GlaxoSmithKline
Enrollment: 316
Locations: 112
Primary Endpoint: Confirmed Objective Response Rate (ORR) compared between Sub studies and Dostarlimab monotherapy
Status: Active, Not Recruiting
Last Updated: 23 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

November 14, 2023

End Date

December 31, 2027

Last Updated

23 days ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

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 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.)

Arms & Interventions

Sub study 4: Dostarlimab and remzistotug

Intervention: Remzistotug

Sub study 3: Dosarlimab and Belrestotug and nelistotug

Intervention: Nelistotug

Sub study 4: Dostarlimab and remzistotug

Intervention: Dostarlimab

Sub study 2: Dostarlimab and nelistotug

Intervention: Nelistotug

Sub study 1: Dostarlimab and Belrestotug

Intervention: Dostarlimab

Sub study 2: Dostarlimab and nelistotug

Intervention: Dostarlimab

Dostarlimab Monotherapy

Intervention: Dostarlimab

Sub study 1: Dostarlimab and Belrestotug

Intervention: Belrestotug

Sub study 3: Dosarlimab and Belrestotug and nelistotug

Intervention: Belrestotug

Sub study 3: Dosarlimab and Belrestotug and nelistotug

Intervention: Dostarlimab

Outcomes

Primary Outcomes

Confirmed Objective Response Rate (ORR) compared between Sub studies and Dostarlimab monotherapy

Time Frame: 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 Outcomes

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)
Rate of Circulating Tumor Deoxyribonucleic Acid (ctDNA) Molecular Response(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)