Neoplasms, Lung
Conditions
Keywords
Small Cell Lung Cancer (SCLC), GSK5764227, Topotecan
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."
Interventions
DRUGTopotecan
Topotecan will be administered
BIOLOGICALGSK5764227
GSK5764227 will be administered
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 |
| 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 |
| 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 |
| 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 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 AEs leading to dose modifications or study intervention discontinuation | 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. |
| 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. |
| Observed PK concentrations of GSK5764227 (conjugated antibody and small molecule payload) | Up to approximately 161 weeks | — |
| Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb) | Up to approximately 161 weeks | — |
| Titers of ADA against GSK5764227 | Up to approximately 161 weeks | — |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Finland, France, Germany, Greece, Ireland, Israel, Italy, Japan, Mexico, Poland, Portugal, Romania, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed