A Study of MHB088C Injection Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer

A Phase 3, Multicenter, Randomized, Open-label Study of MHB088C for Injection Versus Treatment of Physician's Choice (TPC) in Comparing the Efficacy and Safety in Subjects With Relapsed Small Cell Lung Cancer (SCLC)

This study was designed to compare the efficacy and safety of MHB088C for Injection with treatment of physician's choice (TPC) in participants with relapsed small cell lung cancer (SCLC).

The primary objective of this study is to assess whether treatment with MHB088C for Injection improves prolongs overall survival (OS) compared with treatment of physician's choice among participants with relapsed SCLC.

The secondary objectives of the study are to further evaluate the efficacy/safety of MHB088C for Injection, immunogenicity of MHB088C, and characterize the pharmacokinetics of MHB088C.

Inclusion Criteria:

Participants must meet all the following criteria to be eligible for randomization into the study:

1. Voluntarily consent to participate in this study and sign the informed consent form.
2. Adults ≥18 years, regardless of gender.
3. ECOG performance status score of 0-1.
4. Estimated survival time of more than 3 months.
5. Capable of understanding trial requirements, willing and able to comply with trial and follow-up procedures.
6. Has histologically or cytologically documented small cell lung cancer (SCLC).
7. Extensive-stage SCLC with disease progression after at least two cycles of platinum-based and PD-1/L1 systemic therapy, with no more than two prior lines of therapy. Prior PD-1/L1 systemic therapy was allowed to use with or without platinum-based regimens.
8. Agrees to provide pre-treatment tumor tissue samples for retrospective analysis of B7-H3 expression and other biomarkers.
9. Has at least 1 measurable lesion according to RECIST v1.1 as assessed by the investigator.
10. Sufficient bone marrow and organ function.

Exclusion Criteria:

Participants who meet any of the following criteria will be disqualified from entering the study:

1. Diagnosis of other primary malignancies within 5 years prior to signing the informed consent form.
2. Prior pathological diagnosis of combined SCLC, or any transformed non-small cell lung cancer or transformed SCLC.
3. Receipt of chemotherapy within 4 weeks prior to the first administration of study drug, or receipt of radiotherapy, biologics, endocrine therapy, immunotherapy, or other anti-tumor therapy within 4 weeks prior to the first dose.
4. Previous or ongoing treatment with topoisomerase I inhibitors, including antibody-drug conjugates (ADCs) containing topoisomerase I inhibitor payloads.
5. Brain metastases (unless asymptomatic and stable for more than 4 weeks prior to randomization); presence of leptomeningeal metastases or brainstem metastases; spinal cord compression (identified via imaging, regardless of symptoms).
6. Bone marrow metastasis.
7. Prior B7-H3-targeted therapy.
8. Has uncontrolled or significant cardiovascular disease.
9. Moderate-to-severe pulmonary disease significantly impairing lung function, including idiopathic pulmonary fibrosis, autoimmune/connective tissue disorders with lung involvement, or prior pneumonectomy.
10. Has history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening.
11. Moderate or severe pulmonary diseases severely affecting lung function.
12. Active tuberculosis, autoimmune diseases not in clinical remission, other acquired or congenital immunodeficiency diseases, or history of allogeneic stem cell, bone marrow, or organ transplantation.
13. Serious infections within 4 weeks before the first dose, including but not limited to those requiring systemic antibiotic therapy, bacteremia, or severe pneumonia.
14. Clinically uncontrolled third-space effusion requiring intervention, including pleural or peritoneal effusions.
15. Known hypersensitivity to investigational product components, analogues, or control drugs (e.g., topotecan, irinotecan, paclitaxel).
16. Pregnant or lactating women, or women/men intending to conceive.