Neoplasms, Lung
Conditions
Keywords
Small Cell Lung Cancer (SCLC), Risvutatug Rezetecan, Topotecan, EMBOLD SCLC-301, Ris-Rez
Brief summary
In this study researchers are testing Risvutatug rezetecan also known as (Ris-Rez) a new medicine that targets specific proteins (B7-H3) on cancer cells, thereby reducing the cancer's ability to grow and spread. This study specifically aims to evaluate how well Ris-Rez works in treating relapsed SCLC compared to standard treatment topotecan, by checking whether Ris-Rez makes cancers smaller or disappear completely and if it helps participants live longer. The study is also assessing whether Ris-Rez 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 Ris-Rez and the other receiving topotecan.
Interventions
BIOLOGICALRis-Rez
Ris-Rez will be administered
DRUGTopotecan
Topotecan 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 for at least 2 cycles of therapy and a chemotherapy free-interval of \>30 days, with documented progression. Participants with prior tarlatamab treatment in either the first- or second-line ES-SCLC setting are eligible. * 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 adequate organ function and 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. * Limited stage small cell lung cancer at diagnosis * 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 significant pulmonary disease or respiratory impairment (e.g., uncontrolled asthma/COPD, restrictive lung disease), * Has active Hepatitis B or Hepatitis C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 113 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 |
|---|---|---|
| Number of participants with a change from baseline in laboratory parameters (hematology and clinical chemistry) | Baseline (Day -1) and up to approximately 139 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 139 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 139 weeks | Number of participants will be assessed. |
| Observed PK concentrations of Ris-Rez (conjugated antibody and small molecule payload) | Up to approximately 139 weeks | — |
| Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb) | Up to approximately 139 weeks | — |
| Titers of ADA against Ris-Rez | Up to approximately 139 weeks | — |
| Participant reported experience with study treatment | Up to approximately 139 weeks | Participant reported outcomes assessing symptoms, daily functioning, and overall health status during study treatment will be measured using validated questionnaires |
| Number of participants with AEs leading to dose modifications or study intervention discontinuation | Up to approximately 139 weeks | — |
| Number of participants with Adverse events (AEs), Serious Adverse Events (SAEs) and Adverse events of special interest (AESIs) by severity | Up to approximately 139 weeks | — |
| Time to brain progression | Up to approximately 139 weeks | Time to brain progression is defined as the time from the date of randomization to the date of first documented brain PD per modified RANO-BM BICR assessment in participants with a history of brain metastasis or presence of brain metastasis at baseline. |
| Objective Response Rate (ORR) | Up to approximately 139 weeks | ORR is defined as the percentage of participants with a confirmed complete (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by investigator/Blinded Independent Central Review (BICR) assessment |
| Duration of Response (DoR) | Up to approximately 139 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 139 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) for a duration of at least 11 weeks, per RECIST 1.1 by investigator/BICR assessment |
| Brain PFS | Up to approximately 139 weeks | Brain PFS is defined as the time from the date of randomization to the date of first documented PD per modified Response assessment in neuro-oncology (RANO-BM) by BICR assessment or death from any cause, whichever occurs first in participants with history of brain metastasis or presence of brain metastasis at baseline |
| Brain DoR | Up to approximately 139 weeks | Brain DoR is defined as the time from the first documented objective response (CR/PR according to modified RANO-BM BICR assessment) until the time of first documentation of disease progression or death, whichever occurs first, in participants with a history of brain metastasis or presence of brain metastasis at baseline |
| Brain ORR | Up to approximately 139 weeks | Brain ORR is defined as the percentage of participants with confirmed brain CR or confirmed brain PR per modified RANO-BM BICR assessment in participants with a history of brain metastasis or presence of brain metastasis at baseline |
| Number of participants with a change from baseline in vital signs | Baseline (Day -1) and up to approximately 139 weeks | Number of participants will be assessed. |
| 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 modified RANO-BM BICR assessment in participants with a history of brain metastasis or presence of brain metastasis at baseline |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Mexico, Poland, Portugal, Romania, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed