A Prospective, Single-Arm, Exploratory Study of IBI363 in ES-SCLC Patients After Immunotherapy Progression

Inclusion criteria

• Age 18 to 75 years (inclusive), male or female.
• Histologically confirmed small cell lung cancer (SCLC).
• Extensive-stage SCLC refractory to 2 to 3 prior lines of systemic anti-tumor therapy, which must have included PD-1/PD-L1 immunotherapy.
• At least one measurable target lesion as per RECIST 1.1 criteria. The target lesion must be measurable (longest diameter ≥10 mm at baseline, or for lymph nodes, short-axis diameter ≥15 mm) and not have been previously irradiated, or have demonstrated clear progression after local therapy. Lesions solely within the brain are not acceptable as target lesions.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 3 months.
• Adequate organ function,
• Fertile patients (male and female) must agree to use highly effective contraception (e.g., hormonal, barrier methods, or abstinence) with their partner during the trial and for at least 6 months after the last dose. A serum pregnancy test for women of childbearing potential must be negative within 7 days prior to the first study dose.
• Subjects must provide written informed consent before initiating any study-specific procedures.

Exclusion criteria

• Histological diagnosis of combined small cell lung cancer (e.g., mixed SCLC and NSCLC), transformed non-small cell lung cancer (e.g., SCLC transformed from NSCLC), or transformed SCLC (e.g., NSCLC transformed to SCLC).
• Known history of hypersensitivity (≥ Grade 3 per CTCAE v5.0) to any antibody-based therapeutic agent, or known hypersensitivity to the active substance or inactive excipients of the investigational product.
• Major surgical procedure (excluding needle biopsy) or significant trauma within 4 weeks prior to the first dose of study treatment, or anticipation of the need for elective surgery during the study period.
• Systemic corticosteroid therapy (>10 mg/day prednisone or equivalent) within 14 days prior to the first dose of study treatment, with the following exceptions: topical, ocular, intra-articular, intranasal, or inhaled corticosteroids; short-term prophylactic use (e.g., for contrast media allergy); or treatment with other immunosuppressive agents within 4 weeks.
• Use of immunomodulatory drugs (e.g., thymosin, interleukin-2, interferon) within 14 days prior to the first dose of study treatment.
• Administration of a live attenuated vaccine within 4 weeks prior to the first dose of study treatment.
• Prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation.
• Adverse events from prior anti-tumor therapy have not recovered to ≤ Grade 1 per CTCAE v5.0 or the levels specified in the inclusion criteria (with the exception of toxicities deemed not to pose a safety risk by the investigator, such as alopecia, Grade 2 peripheral neuropathy, or hypothyroidism stable on hormone replacement therapy).
• Untreated brain metastases (subjects with treated brain metastases are eligible if clinically stable for ≥4 weeks prior to the first dose, off steroid therapy for ≥2 weeks, and without significant peritumoral edema on imaging); leptomeningeal metastasis or brainstem metastasis; spinal cord compression (radiologically identified, regardless of symptoms).
• Active infection requiring intravenous anti-infective therapy at the time of screening.
• History of immunodeficiency, including a positive test for human immunodeficiency virus (HIV).
• Active hepatitis B (HBsAg positive and HBV-DNA ≥1000 IU/mL or copies/mL) or active hepatitis C (HCV antibody positive and HCV RNA above the upper limit of normal).
• Interstitial lung disease (except for radiation-induced fibrosis not requiring corticosteroid therapy).
• Significant cardiovascular and cerebrovascular disease history
• Active autoimmune disease, or history of autoimmune disease with potential for recurrence (exceptions include well-controlled autoimmune thyroiditis, type I diabetes, vitiligo, childhood atopic dermatitis resolved, psoriasis not requiring systemic therapy in the past 2 years, etc.).
• Prior history of ≥ Grade 3 immune-related adverse event (irAE) or ≥ Grade 2 immune-related myocarditis associated with prior immunotherapy.
• History of other malignancies, except for those cured for ≥2 years, such as non-melanoma skin cancer, localized prostate cancer, or carcinoma in situ (e.g., cervical carcinoma in situ).
• Pleural effusion or ascites requiring therapeutic intervention (subjects with stable effusion not requiring drainage or stable for ≥1 week after drainage may be eligible); pericardial effusion (asymptomatic, minimal effusion not requiring intervention per investigator's assessment is allowed). If intra-cavitary anti-tumor agents were used during drainage, a washout period of at least 5 half-lives or 21 days (whichever is shorter) must be completed prior to the first dose.
• Known history of alcohol or drug dependence.
• History of psychiatric disorders or anticipated poor compliance.
• Pregnancy or lactation.
• Any other condition deemed by the investigator to potentially compromise the subject's safety or compliance, or make the subject unsuitable for the study.