A Study of GSK5764227 in Participants With Relapsed Small Cell Lung Cancer (SCLC)

Not Applicable

Recruiting

• Conditions: Neoplasms, Lung
• Interventions: Biological: GSK5764227; Drug: Topotecan

• Registration Number: NCT07099898
• Lead Sponsor: GlaxoSmithKline

Brief Summary

"In this study researchers are testing GSK5764227, a new medicine that targets specific proteins (B7-H3) on cancer cells, thereby reducing the cancers ability to grow and spread. This study specifically aims to evaluate how well GSK5764227 works in treating relapsed SCLC compared to standard treatment topotecan, by checking whether GSK5764227 makes cancers smaller or disappear completely and if it helps participants live longer. The study is also assessing whether GSK576227 is safe and tolerated well by participants compared to topotecan and provide a better understanding of the main side effects of both drugs. Participants with relapsed SCLC will be randomly divided into two groups: one group receiving GSK5764227 and the other receiving topotecan."

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-07-30
• Study First Submitted QC: 2025-07-30
• Study First Posted: 2025-08-01
• Study Start: 2025-08-11
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-25
• Last Update Posted: 2025-09-26
• Primary Completion: 2026-09-02
• Study Completion: 2028-09-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

• Adults >18 or the minimum legal adult age at the time the informed consent form is signed
• Has histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC).
• Has received 1 prior platinum-based systemic therapy with a PD- (L)1 inhibitor with at least 2 cycles of therapy and a chemotherapy free-interval of >30 days, with documented progression
• Has at least 1 target lesion per RECIST 1.1, as determined by the investigator.
• Is capable of giving signed informed consent, including compliance with the requirements and restrictions listed in the ICF and in the protocol.
• Has an ECOG performance status of 0 or 1

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

• Pathological diagnosis of complex SCLC or transformed SCLC.
• Has received any prior therapy with an Antibody-drug conjugate (ADC) with a Topoisomerase-1 (TOPO1)-inhibitor payload or treatments targeting B7-H3.
• Has known sensitivity to study intervention components or excipients or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
• Has severe, uncontrolled or active cardiovascular disorders.
• Has clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose.
• Known active infectious diseases requiring systemic treatment or known Human immunodeficiency virus (HIV).
• Has symptomatic brain metastases or untreated progression exclusively due to brain metastasis during or after the last treatment prior to screening, evidence of leptomeningeal/meningeal/brainstem metastasis or evidence of spinal cord metastases.
• Has any evidence of current interstitial lung disease or pneumonitis or a prior history of ILD or non-infectious pneumonitis requiring high dose steroids.
• Has documented Hepatitis B or Hepatitis C

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GSK5764227	GSK5764227	-
Topotecan	Topotecan	-

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to approximately 55 weeks	ORR is defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Blinded independent central review (BICR) assessment
Overall Survival (OS)	Up to approximately 55 weeks	OS is defined as the time from the date of randomization to the date of death by any cause

Secondary Outcome Measures

Name	Time	Method
Brain PFS	Up to approximately 161 weeks	Brain PFS is defined as the time from the date of randomization to the date of first documented PD per Response assessment in neuro-oncology (RANO-BM) by Response Evaluation Criteria in Solid Tumors by blinded independent central review (RANO-BICR) assessment or death from any cause, whichever occurs first in participants with a history of brain metastasis
Time to brain progression	Up to approximately 161 weeks	Time to brain progression is defined as the time from the date of randomization to the date of first documented brain PD per RANO-BM by RANO-BICR assessment
Number of participants with a change from baseline in cardiac function [Electrocardiogram (ECG)	Baseline (Day -1) and up to approximately 161 weeks	Number of participants will be assessed.
Number of participants with a change from baseline in Eastern Cooperative Oncology Group (ECOG) performance status	Baseline (Day -1) and up to approximately 161 weeks	Number of participants will be assessed.
Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb)	Up to approximately 161 weeks
ORR by investigator assessment	Up to approximately 161 weeks	ORR is defined as the percentage of participants with a confirmed CR or confirmed PR per RECIST 1.1 by investigator assessment
Duration of Response (DoR)	Up to approximately 161 weeks	DoR is defined as the time from the date of first documented objective response (CR or PR) per RECIST 1.1 by \[investigator/BICR\] assessment to the date of first documented PD per RECIST 1.1 by \[investigator/BICR\] assessment or death due to any cause, whichever comes first
Progression-free survival (PFS)	Up to approximately 161 weeks	PFS is defined as the time from the date of randomization to the date of first documented Progressive disease (PD) per RECIST 1.1 by \[investigator/BICR\] assessment or death from any cause, whichever occurs first
Disease control rate (DCR) 12	Up to approximately 11 weeks	DCR12 is defined as the percentage of participants who have a Best objective response (BOR) of confirmed CR, confirmed PR, or Stable Disease (SD) after the date of randomization, per RECIST 1.1 by \[investigator/BICR\] assessment
Brain DoR	Up to approximately 161 weeks	Brain DoR is defined as the time from the first documented objective response (CR/PR according to RANO-BM by RANO-BICR assessment) until the time of first documentation of disease progression or death, whichever occurs first, in participants with a history of brain metastasis
Brain ORR	Up to approximately 161 weeks	Brain ORR is defined as the percentage of participants with confirmed brain CR or confirmed brain PR per RANO-BM by RANO-BICR assessment
Number of participants with AEs leading to dose modifications or study intervention discontinuation	Up to approximately 161 weeks
Titers of ADA against GSK5764227	Up to approximately 161 weeks
Brain DCR12	Up to approximately 11 weeks	Brain DCR12 is defined as the percentage of participants with an intracranial BOR of confirmed CR, confirmed PR or SD after the date of randomization, per RANO-BM by RANO-BICR assessment
Number of participants with Adverse events (AEs), Serious Adverse Events (SAEs) and Adverse events of special interest (AESIs) by severity	Up to approximately 161 weeks
Number of participants with a change from baseline in vital signs	Baseline (Day -1) and up to approximately 161 weeks	Number of participants will be assessed.
Number of participants with a change from baseline in laboratory parameters (hematology and clinical chemistry)	Baseline (Day -1) and up to approximately 161 weeks	Number of participants will be assessed.
Observed PK concentrations of GSK5764227 (conjugated antibody and small molecule payload)	Up to approximately 161 weeks

Trial Locations

Locations (1)

GSK Investigational Site; 🇰🇷 Ulsan, South Korea