A Phase III Study of YL201 in Relapsed Small Cell Lung Cancer

A Multicenter, Randomized, Controlled, Open-label, Phase III Study to Compare the Efficacy and Safety of YL201 Versus Topotecan Hydrochloride in Subjects With Relapsed Small Cell Lung Cancer

This study was designed to compare the efficacy and safety of YL201 with Topotecan Hydrochloride in subjects with relapsed small cell lung cancer (SCLC).

The primary objective of this study is to assess whether treatment with YL201 prolongs overall survival (OS) compared with treatment of topotecan hydrochloride among subjects with relapsed SCLC.

The secondary objectives of the study are to further evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of YL201, and the correlation between B7-H3 expression level and the efficacy of YL201.

Inclusion Criteria:

1. Sign and date the informed consent form prior to the start of any study-specific qualification procedures.
2. Aged ≥18 and ≤75 years, male or female.
3. ECOG PS 0 or 1.
4. Life expectancy ≥ 3 months.
5. Histologically or cytologically confirmed SCLC. Subjects with combined SCLC or any transformed SCLC are not eligible.
6. Has limited-stage or extensive-stage disease at study entry, with progression on or after first-line platinum-based therapy (at least 2 cycles).
7. At least one measurable lesion according to RECIST version 1.1.
8. Subjects are willing to provide tumor tissue (freshly obtained or archived) for detection of B7-H3 expression.
9. Adequate organ function.

Exclusion Criteria:

1. History of other malignant tumors within 5 years prior to the first dose of study drug. Subjects cured by radical treatment are not included, such as basal cell carcinoma, squamous cell carcinoma of skin, superficial bladder cancer, carcinoma in situ of the cervix, or breast cancer in situ.
2. Previously received B7-H3-targeted therapy, including antibody, antibody-drug conjugate (ADC), and chimeric antigen receptor T cell (CAR-T).
3. Previously received treatment with a topoisomerase I inhibitor or an ADC consisting of a topoisomerase I inhibitor.
4. Inadequate washout period for prior anti-tumor treatment before the first dose of study drug.
5. Received systemic steroids or other immunosuppressive therapy within 2 weeks before the first dose of study drug.
6. Received any live vaccine within 4 weeks before the first dose of study drug or intend to receive a live vaccine during the study.
7. Presence of brain stem or meningeal metastases, spinal cord metastases or compression.
8. Presence of central nervous system (CNS) metastasis. Participants with treated brain metastases are eligible if the metastases are asymptomatic and stable, and no immediate local or systemic treatment is needed within 2 weeks before the first dose.
9. Presence of pleural effusion, pericardial effusion, or ascites with clinical symptoms or requiring repeated drainage.
10. Has an uncontrolled concurrent disease.
11. Presence of severe uncontrolled cardiovascular disorder.
12. History of interstitial lung disease (ILD) or pneumonitis that required corticosteroids, or current ILD/pneumonitis
13. Concomitant pulmonary disorder leading to clinically severe respiratory impairment.
14. Chronic autoimmune or inflammatory diseases requiring or receiving systemic therapy within 2 years prior to the first dose.
15. Serious infections within 4 weeks prior to the first dose.
16. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
17. Unresolved toxicities from previous antitumor therapy.
18. Known hypersensitivity to any component of any study drug; history of severe allergy or known history of serious hypersensitivity to other monoclonal antibodies or recombinant protein products, or history of severe infusion reactions.
19. Pregnancy, breastfeeding, or women planning to become pregnant or breastfeed during the study.
20. Any illness, medical condition, organ system dysfunction, or social situation deemed by the investigator to be likely to interfere with a subject's ability to sign informed consent, adversely affect the subject's ability to cooperate and participate in the study, or compromise the interpretation of study results.