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

Phase 3RecruitingNCT07099898

GlaxoSmithKline420 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

420

Conditions

Neoplasms, Lung

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (132)

GSK Investigational Site

Los Angeles, California, United States

RECRUITING

GSK Investigational Site

Wilson, North Carolina, United States

RECRUITING

GSK Investigational Site

Mar del Plata, Buenos Aires, Argentina

RECRUITING

GSK Investigational Site

Buenos Aires, Argentina

Outcomes

Primary Outcomes

Overall Survival (OS)

OS is defined as the time from the date of randomization to the date of death by any cause

Time frame: Up to approximately 113 weeks

Secondary Outcomes

Objective Response Rate (ORR)

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

Time frame: Up to approximately 139 weeks

Duration of Response (DoR)

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

Time frame: Up to approximately 139 weeks

Progression-free survival (PFS)

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

Time frame: Up to approximately 139 weeks

Disease control rate (DCR) 12

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

Time frame: Up to approximately 11 weeks

Brain PFS

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

Time frame: Up to approximately 139 weeks

Brain DoR

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

Time frame: Up to approximately 139 weeks

Brain ORR

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

Time frame: Up to approximately 139 weeks

Brain DCR12

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

Time frame: Up to approximately 11 weeks

Time to brain progression

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.

Time frame: 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

Time frame: Up to approximately 139 weeks

Number of participants with AEs leading to dose modifications or study intervention discontinuation

Time frame: Up to approximately 139 weeks

Number of participants with a change from baseline in vital signs

Number of participants will be assessed.

Time frame: Baseline (Day -1) and up to approximately 139 weeks

Number of participants with a change from baseline in laboratory parameters (hematology and clinical chemistry)

Number of participants will be assessed.

Time frame: Baseline (Day -1) and up to approximately 139 weeks

Number of participants with a change from baseline in cardiac function [Electrocardiogram (ECG)

Number of participants will be assessed.

Time frame: Baseline (Day -1) and up to approximately 139 weeks

Number of participants with a change from baseline in Eastern Cooperative Oncology Group (ECOG) performance status

Number of participants will be assessed.

Time frame: Baseline (Day -1) and up to approximately 139 weeks

Observed PK concentrations of Ris-Rez (conjugated antibody and small molecule payload)

Time frame: Up to approximately 139 weeks

Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb)

Time frame: Up to approximately 139 weeks

Titers of ADA against Ris-Rez

Time frame: Up to approximately 139 weeks

Participant reported experience with study treatment

Participant reported outcomes assessing symptoms, daily functioning, and overall health status during study treatment will be measured using validated questionnaires

Time frame: Up to approximately 139 weeks

Central Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718 GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com