QLC5508 vs. Chemotherapy in Pretreated Advanced or Metastatic Esophageal Squamous Cell Carcinoma

Inclusion criteria

• Voluntarily consent to participate in this study and sign the informed consent form.
• Males and females aged ≥18 years old;
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 within 7 days before the first dose;
• Estimated survival time of more than 3 months.
• A serum pregnancy test must be performed within 7 days prior to randomization for premenopausal women of childbearing potential, and the result must be negative and must not be lactating;
• All enrolled patients and the partners should take adequate barrier contraception during the entire treatment cycle and for 6 months after the end of treatment.
• Capable of understanding trial requirements, willing and able to comply with trial and follow-up procedures.
• Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0 (v6.0);
• Has histologically or cytologically documented unresectable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) according to American Joint Committee on Cancer 8th edition staging system on ESCC.

• Has at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) as assessed by the investigator.
• Sufficient bone marrow and organ function.

Exclusion criteria

• Diagnosis of other primary malignancies within 5 years prior to signing the informed consent form.
• Having histologically or cytologically confirmed adenosquamous carcinoma subtype.
• Brain metastases (unless asymptomatic and no progression confirmed by imaging ≥4 weeks prior to randomization);
• Presence of leptomeningeal metastases or brainstem metastases;
• Spinal cord compression (identified via imaging, regardless of symptoms);
• Previous or ongoing treatment with topoisomerase I inhibitors
• Having previously received B7-H3-targeted therapy.
• Being ineligible to any chemotherapies in the control arm due to prior progression or intolerance.
• Insufficient washout of prior anticancer therapies prior to randomization.
• Having underwent major organ surgery (excluding biopsy) or significant trauma within 4 weeks prior to randomization;
• Requiring elective surgery during the study.
• Having received live vaccine or live attenuated vaccine within 4 weeks before study randomization.
• Having received treatment with systemic corticosteroids (prednisone at >10 mg/day, or similar drugs at equivalent dose) or other immunosuppressive agents within 14 days prior to randomization;
• Moderate to severe pulmonary disease significantly impairing lung function, including idiopathic pulmonary fibrosis, autoimmune/connective tissue disorders with lung involvement, or prior pneumonectomy.
• Having a history of interstitial lung disease (ILD)/ non-infectious pneumonitis that required corticosteroids, current ILD/ non-infectious pneumonitis, or suspected ILD/ non-infectious pneumonitis that cannot be ruled out by imaging at screening;
• Active tuberculosis;
• Autoimmune diseases not in clinical remission, other acquired or congenital immunodeficiency diseases,
• A history of allogeneic stem cell, bone marrow, or organ transplantation.
• Serious infections (e.g., bacteremia, or severe pneumonia) within 4 weeks prior to randomization;
• active infection requiring systemic antibiotic therapy within 1 weeks prior to randomization;
• Has positive results in virus serology tests (hepatitis B virus infection participants receiving antiviral treatment other than interferon are allowed to be enrolled);
• Uncontrolled or significant cardiovascular disease.
• Clinically uncontrolled third-space effusion.
• Known hypersensitivity to investigational product components, analogues, or control drugs (e.g., docetaxel, paclitaxel, irinotecan hydrochloride).
• Drug abuse;
• Any other medical conditions that may interfere with study participation or the results of the clinical study as per the discretion of investigator;
• Has alcohol or drug dependence.
• Poor compliance as per investigator discretion;
• Has a history of other serious systemic diseases.