A Study of Belrestotug Plus Dostarlimab Compared With Placebo Plus Pembrolizumab in Previously Untreated Participants With Programmed Death Ligand 1 (PD-L1) High Non-small-cell Lung Cancer (NSCLC)

Phase 3

Active, not recruiting

• Conditions: Lung Cancer, Non-Small Cell
• Interventions: Biological: Pembrolizumab; Biological: Dostarlimab; Drug: Placebo; Biological: Belrestotug

• Registration Number: NCT06472076
• Lead Sponsor: GlaxoSmithKline

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety profile of dostarlimab in combination with belrestotug when compared with pembrolizumab and placebo in participants with previously untreated, unresectable, locally advanced or metastatic PD-L1 high NSCLC. Researchers will compare belrestotug plus dostarlimab with pembrolizumab plus placebo to see if there is meaningful improvement in progression free survival (PFS) and overall survival (OS).

Detailed Description

Not available

Study Timeline

• Study Start: 2024-06-10
• Study First Submitted: 2024-06-18
• Study First Submitted QC: 2024-06-18
• Study First Posted: 2024-06-24
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-14
• Last Update Posted: 2025-07-15
• Primary Completion: 2027-02-02
• Study Completion: 2027-02-02

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

• Has a histologically or cytologically confirmed diagnosis of locally advanced, unresectable NSCLC (not eligible for curative surgery and/or definitive radiotherapy with or without chemotherapy), or Metastatic NSCLC
• Has not received prior systemic therapy for their locally advanced or metastatic NSCLC.
• Provides a fresh tumor tissue sample obtained at the time of or after the initial diagnosis of locally advanced or metastatic NSCLC.
• Has a PD-L1-high (Tumor cells [TC] ≥50%) tumor
• Has measurable disease (at least 1 target lesion) based on RECIST 1.1
• Has an Eastern Cooperative Oncology Group (ECOG) Performance status (PS) score of 0 or 1.
• Has adequate organ function

Exclusion Criteria

• Has NSCLC with a tumor that harbors any of the following molecular alterations:

  1. Epidermal growth factor receptor (EGFR) mutations that are sensitive to available targeted inhibitor therapy
  2. Anaplastic lymphoma kinase (ALK) translocations that are sensitive to available targeted inhibitor therapy
  3. Any other known genomic aberrations or oncogenic driver mutations for which a locally approved targeted therapy is available for first line treatment of locally advanced or metastatic NSCLC.

• Has had surgery within 4 weeks of the first dose of study intervention and has not recovered from AEs (i.e., has any ongoing surgery-related events ≥ Grade 1)/complications related to surgery or has received lung radiation therapy of >30 gray (Gy) within 6 months

• Has received prior therapy with any immune checkpoint inhibitors, including antibodies or drugs targeting PD-(L)1, Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and ITIM domain (TIGIT), or other checkpoint pathways.

• Has never smoked, defined as smoking <100 tobacco cigarettes in a lifetime.

• Has an invasive malignancy or history of invasive malignancy other than the disease under study within the last 5 years, with the exception of those with a negligible risk of metastasis or death and/or treated with expected curative outcome.

• Has symptomatic, untreated, or actively progressin g brain metastases or leptomeningeal disease

• Has autoimmune disease or syndrome (current or history thereof) that required systemic treatment within the past 2 years.

• Has received any live vaccine within 30 days prior to first dose of study intervention.

• Has any history of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis.

• Has symptomatic ascites, pleural effusion, or pericardial effusion.

• Has active inflammatory bowel disease

• Has a history of significant acute or chronic cardiac diagnosis requiring intervention/treatment in the last 6 months.

• Has severe infection or complication thereof 4 weeks prior to randomisation including active tuberculosis.

• Has a history of allogeneic tissue/stem cell transplant or solid organ transplant.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pembrolizumab plus placebo	Pembrolizumab	-
Pembrolizumab plus placebo	Placebo	-
Dostarlimab plus belrestotug	Dostarlimab	-
Dostarlimab plus belrestotug	Belrestotug	-

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to approximately 5 years	OS is defined as the time from the date of randomization to the date of death due to any cause.
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by Blinded independent central review (BICR)	Up to approximately 5 years	PFS as assessed per RECIST v1.1 by BICR is time from date of randomization to date of first documented progressive disease (PD) or death due to any cause, whichever comes first.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with TEAEs or SAEs leading to dose modifications or study intervention discontinuation	Up to approximately 5 years
Duration of Response (DOR)	Up to approximately 5 years	DOR per RECIST v 1.1 by investigator assessment, defined as the time from the date of first confirmed response (CR or PR) to the date of first documented PD or death due to any cause, whichever comes first.
Number of participants with anti-drug antibodies (ADA) against Dostarlimab	Up to approximately 5 years
Molecular Response Rate (MRR)	Up to approximately 5 years	MRR is defined as the percentage of participants with a molecular response (i.e., a greater than or equal to 50% reduction in Circulating tumor deoxyribonucleic acid (ctDNA) levels relative to baseline).
PFS per RECIST 1.1 by investigator assessment	Up to approximately 5 years	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.
Objective Response Rate (ORR)	Up to approximately 5 years	ORR is defined as the percentage of participants achieving confirmed complete response (CR) or confirmed partial response (PR) per RECIST version 1.1 by investigator assessment.
Number of participants with ADA against Belrestotug	Up to approximately 5 years
Time to first subsequent therapy (TFST)	Up to approximately 5 years	TFST is defined as the time from the date of randomization to the date of the first subsequent anticancer therapy or death, whichever occurs first.
Number of Participants with Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)	Up to approximately 5 years
Time to Deterioration (TTD) of lung cancer symptoms	Up to approximately 5 years	TTD of lung cancer symptoms is defined as time from randomization to the first confirmed clinically meaningful deterioration as assessed by the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC SAQ) total score. The NSCLC-SAQ is a 7-item instrument that assesses symptoms relevant to NSCLC. It contains five domains and accompanying items that are identified as symptoms of NSCLC: cough (1 item), pain (2), dyspnea (1), fatigue (2), and appetite (1). The (total) lowest score possible is 0, and the highest (total) score possible is 20. Higher scores indicate more severe symptoms.
TTD in physical functioning	Up to approximately 5 years	TTD in physical functioning is defined as time from randomization to the first confirmed clinically meaningful deterioration as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ C30). The EORTC QLQ C30 is a 30-item questionnaire. Participant responses will be scored in a range of 0-100. A higher value indicates a better level of physical function.

Trial Locations

Locations (1)

GSK Investigational Site; 🇹🇷 Istanbul, Turkey