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NCT Number: NCT07099898

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

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.

Recruiting

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

GSK Investigational Site, Mar del Plata, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ris-Rez

Biological

Ris-Rez will be administered

Topotecan

Drug

Topotecan will be administered

Primary outcomes

  1. Overall Survival (OS)

    Time frame: 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 outcomes

  1. Objective Response Rate (ORR)

    Time frame: 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

  2. Duration of Response (DoR)

    Time frame: 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

  3. Progression-free survival (PFS)

    Time frame: 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

  4. Disease control rate (DCR) 12

    Time frame: 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

  5. Brain PFS

    Time frame: 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

  6. Brain DoR

    Time frame: 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

  7. Brain ORR

    Time frame: 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

  8. Brain DCR12

    Time frame: 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

  9. Time to brain progression

    Time frame: 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.

  10. 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

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

    Time frame: Up to approximately 139 weeks

  12. Number of participants with a change from baseline in vital signs

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

    Number of participants will be assessed.

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

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

    Number of participants will be assessed.

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

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

    Number of participants will be assessed.

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

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

    Number of participants will be assessed.

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

    Time frame: Up to approximately 139 weeks

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

    Time frame: Up to approximately 139 weeks

  18. Titers of ADA against Ris-Rez

    Time frame: Up to approximately 139 weeks

  19. Participant reported experience with study treatment

    Time frame: 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

Study contacts

Contact information is provided by the study sponsor or research team.

EU GSK Clinical Trials Call Center

CONTACT

[email protected]

+44 (0) 20 89904466

US GSK Clinical Trials Call Center

CONTACT

[email protected]

877-379-3718

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

Phase 3, Multicenter, Randomized, Open-label Clinical Study of GSK5764227, a B7-H3 Antibody Drug Conjugate (ADC), Compared With Topotecan in Participants With Relapsed Small Cell Lung Cancer (SCLC)

Important dates

Study start
2025
Primary completion
2027
Study completion
2029
First posted
Aug 1, 2025
Registry last updated
May 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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