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.

Eligibility

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