A Single-arm, Open-label, Phase II Study to Evaluate Efficacy, Safety and Pharmacokinetics of HLX10 + Chemotherapy in Patients With ES-SCLC

Inclusion criteria

• Voluntary participation in clinical studies; fully understand, be informed about the study and have signed the informed consent form (ICF); willingness to follow and ability to complete all trial procedures.
• Male or female aged ≥ 18 years at the time of signing the ICF.
• Histologically or cytologically diagnosed with ES-SCLC (according to the Veterans Administration Lung Study Group staging system).
• No prior systemic therapy for ES-SCLC (including systemic chemotherapy, molecular targeted therapy, biological therapy, and other investigational therapies, etc.).
• Subjects who have received chemoradiotherapy for previous limited stage SCLC must be treated with curative intent and have a treatment-free interval of at least 6 months from the last course of chemotherapy, radiotherapy, or chemoradiotherapy to the diagnosis of extensive stage SCLC.
• At least one measurable lesion as assessed by the IRRC according to RECIST 1.1 within 4 weeks prior to first dose.

Exclusion criteria

• Histologically or cytologically confirmed mixed SCLC.
• Other active malignancies within 5 years or at the same time. Localized tumors that have been cured, such as basal cell carcinoma, squamous-cell skin cancer, superficial bladder cancer, prostate carcinoma in situ, cervical cancer in situ and breast cancer in situ are acceptable.
• Subjects who are preparing for or have received an organ or bone marrow transplant.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Subjects with indwelling catheters are allowed regardless of drainage frequency.
• Subjects with known or documented active CNS metastases and/or carcinomatous meningitis at screening. However, the following subjects are allowed to be enrolled: 1) Subjects with asymptomatic brain metastases (i.e., no progressive central nervous system symptoms caused by brain metastases, no requirement for corticosteroids, and lesion size ≤ 1.5 cm) may be included, but are required to receive regular brain imaging as a site of lesion. 2) Subjects with treated brain metastases which have been stable for at least 2 months (as confirmed by 2 radiological examinations at least 4 weeks apart after treatment of brain metastases), with no evidence of new or enlarging brain metastases, and with discontinued steroids 3 days prior to study drug administration. (Stable brain metastases here should be confirmed before the first dose of the study drug.).
• Subjects with spinal cord compression that has not been radically treated with surgery and/or radiotherapy.
• Subjects with myocardial infarction within half a year before the first dose of the study drug, poorly controlled arrhythmia (including QTc intervals ≥ 450 ms for males and ≥ 470 ms for females) (QTc intervals are calculated by Fridericia's formula).
• Class III to IV cardiac insufficiency according to NYHA classification or a left ventricular ejection fraction < 50% by cardiac color Doppler.
• Subject has uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN).
• Subject with peripheral neuropathy ≥ Grade 2 by CTCAE.
• Human immunodeficiency virus (HIV) infection, positive test for HIV antibody.
• Active or latent pulmonary tuberculosis.
• Subjects with previous and concurrent interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis and severe impaired pulmonary function that may interfere with the detection and management of suspected drug-related pulmonary toxicity, as judged by the investigator.
• Hepatitis B (positive test for HBsAg or HBcAb and positive test for HBV-DNA) or Hepatitis C (positive tests for HCV antibody and HCV-RNA). Hepatitis B and C coinfection (positive test for HBsAg or HBcAb and positive test for HCV antibody).
• Known active or suspected autoimmune diseases. Subjects in a stable state with no need for systemic immunosuppressant therapy are allowed to enroll.