Prospective registration

A multicenter, randomized, open-label, controlled, phase III clinical study to evaluate the efficacy and safety of HS-20093 for injection combined with adebrelimab versus docetaxel in patients with driver gene-negative advanced or metastatic non-squamous non-small cell lung cancer who have progressed or relapsed after prior standard platinum-based chemotherapy.

A multicenter, randomized, open-label, controlled phase III clinical study (by center) to evaluate HS-20093 for injection combined with adebrelimab versus docetaxel in patients with driver gene-negative advanced or metastatic non-squamous non-small cell lung cancer.

A multicenter, randomized, open-label, controlled, phase III clinical study to evaluate the efficacy and safety of HS-20093 for injection combined with adebrelimab versus docetaxel in patients with driver gene-negative advanced or metastatic non-squamous non-small cell lung cancer who have progressed or relapsed after prior standard platinum-based chemotherapy.

Zhao Yanhui 

Lin Wu 

Building 11, No. 3728 Jinke Road, China (Shanghai) Pilot Free Trade Zone

283 Tongzipo Road, Yuelu District, Changsha City

Shanghai Hansoh Biomedical Technology Co., Ltd.

Hunan Cancer Hospital

Yes

Medical Ethics Review Committee of Hunan Cancer Hospital

Yang Feng

283 Tongzipo Road, Yuelu District, Changsha City

Hunan Cancer Hospital

283 Tongzipo Road, Yuelu District, Changsha City

Shanghai Hansoh Biomedical Technology Co., Ltd.

Advanced or metastatic non-squamous non-small cell lung cancer

Interventional study

3

Parallel 

Primary Objectives:To evaluate progression-free survival (PFS) (assessed by blinded independent central review) and overall survival (OS) of HS-20093 combined with adebrelimab versus docetaxel in patients with driver gene-negative advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) who have progressed or relapsed after prior standard platinum-based chemotherapy.# Secondary Objectives:1. To evaluate other efficacy endpoints of HS-20093 combined with adebrelimab versus docetaxel in patients with driver gene-negative advanced or metastatic nsq-NSCLC who have progressed or relapsed after prior standard platinum-based chemotherapy.2. To evaluate the safety of HS-20093 combined with adebrelimab versus docetaxel in patients with driver gene-negative advanced or metastatic nsq-NSCLC who have progressed or relapsed after prior standard platinum-based chemotherapy.# Exploratory Objectives:1. To evaluate the pharmacokinetic (PK) profile of HS-20093 combined with adebrelimab in patients with driver gene-negative advanced or metastatic nsq-NSCLC who have progressed or relapsed after prior standard platinum-based chemotherapy.2. To evaluate the immunogenicity of HS-20093 combined with adebrelimab in patients with driver gene-negative advanced or metastatic nsq-NSCLC who have progressed or relapsed after prior standard platinum-based chemotherapy.3. To explore the relationship between PK exposure of HS-20093 for injection and/or adebrelimab and clinical ef

1. Aged >= 18 years at the time of signing the informed consent form (ICF), with no gender restriction. 2. Voluntarily participate in this clinical trial, understand the study procedures, be able to provide written signature on the ICF, and agree to comply with all requirements specified in this clinical trial protocol. 3. Histologically or cytologically confirmed advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) (Stage IIIB/IIIC/IV, based on AJCC Cancer Staging Manual, 9th edition). Patients must have experienced disease progression or relapse after receiving first-line standard systemic therapy with platinum-based chemotherapy for advanced disease, and be considered eligible for this study by the investigator. Prior radical-intent treatment for locally advanced disease (including neoadjuvant/adjuvant therapy), with disease recurrence or progression occurring within 6 months after the last chemotherapy or last radiotherapy, may be regarded as first-line advanced therapy. If a patient is intolerant to platinum-based chemotherapy, enrollment may be permitted following investigator assessment and documentation of supporting rationale. 4. Provide a valid genetic testing report confirming the absence of the following gene mutations: sensitizing EGFR mutations, ALK fusion mutations, and ROS1 fusion mutations. If a genetic testing report is unavailable or invalid, a sufficient tumor tissue sample must be provided for genetic testing (see Inclusion Criterion 6 for details). Meanwhile, based on available data, there is no evidence of other driver gene mutations. Note: Driver genes refer to mutation types with recommended second-line standard therapies in the current CSCO Guidelines for the Diagnosis and Treatment of Non-Small Cell Lung Cancer, including sensitizing EGFR mutations, EGFR exon 20 insertion mutations, ALK fusion mutations, ROS1 fusion mutations, BRAF V600E mutation, NTRK fusion mutations, MET exon 14 skipping mutation, RET fusion mutations, KRAS G12C mutation, and HER-2 mutations. The list shall be updated according to the mutation types with second-line standard therapies in the annual CSCO Guidelines for Non-Small Cell Lung Cancer. 5. Participants must have at least one measurable target lesion per RECIST version 1.1. Measurable lesions that have received prior radiotherapy and have been confirmed to have progressed after radiotherapy may be considered as target lesions. 6. Fresh tumor tissue samples are preferred (type: formalin-fixed, paraffin-embedded [FFPE] tumor tissue block or FFPE sections). Samples must be sufficient for the central laboratory to perform PD-L1 expression testing, tumor genomic testing (if genetic testing report is unavailable or invalid), and subsequent biomarker analyses (such as B7-H3, if sample volume permits). If fresh samples are unavailable, newly prepared FFPE sections from FFPE tumor tissue blocks within 2 years are acceptable. If tumor tissue samples are older than 2 years, enrollment may be allowed upon agreement with the Sponsor. 7. Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 to 1. 8. Minimum expected survival of more than 12 weeks. 9. Adequate organ function, meeting the following laboratory criteria within 7 days prior to study drug administration: (1) Absolute neutrophil count >= 1.5×10^9/L (no G-CSF corrective/supportive therapy within the previous 2 weeks); (2) Platelet count >= 100×10^9/L (no transfusion corrective/supportive therapy within the previous 1 week); (3) Hemoglobin >= 90 g/L (no erythropoietin administration or red blood cell transfusion within the previous 2 weeks); (4) Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) <= 2.5× upper limit of normal (ULN); in the presence of liver metastases, ALT and/or AST <= 5.0× ULN (no corrective therapy within 7 days prior to blood sampling); (5) Total bilirubin <= 1.5× ULN; in patients with documented Gilbert syndrome (unconjugated hyperbilirubinemia) or liver metastases, total bilirubin <= 3.0× ULN. Per the docetaxel prescribing information, patients with total bilirubin > ULN and/or AST and/or ALT > 3.5× ULN combined with alkaline phosphatase (ALP) > 6× ULN must be excluded (no corrective therapy within 7 days prior to blood sampling); (6) Creatinine <= 1.5× ULN or creatinine clearance >= 50 mL/min (calculated using the Cockcroft-Gault formula in Appendix 12.4 of the protocol); (7) Serum albumin (ALB) >= 28 g/L; (8) International normalized ratio (INR) or prothrombin time <= 1.5× ULN, and activated partial thromboplastin time (APTT) <= 1.5× ULN. If the participant is on anticoagulant therapy, values above these limits are permitted provided anticoagulation is stable and prothrombin time or APTT is within the therapeutic range of the anticoagulant. 10. Absence of any of the following active viral infectious diseases: (1) Hepatitis B (defined as positive hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb] during screening, with detectable hepatitis B virus (HBV) DNA >= 2×10^3 IU/mL. Patients may be enrolled if HBV DNA decreases to below 2×10^3 IU/mL after regular antiviral treatment); (2) Hepatitis C (defined as positive hepatitis C virus antibody [HCV-Ab] and positive HCV-RNA during screening); (3) Human immunodeficiency virus (HIV) infection (defined as positive anti-HIV antibody); (4) Tuberculosis (evidence of active tuberculosis infection within 1 year); (5) Syphilis (both positive treponemal and non-treponemal antibodies). 11. Female participants must have a negative serum pregnancy test within 7 days prior to the first dose, or be considered non-pregnant by meeting one of the following criteria: (1) Postmenopausal (see Appendix 12.7 for detailed definition); (2) Premenarchal females; (3) Premenopausal females with one of the following documented conditions: 1) Total hysterectomy 2) Bilateral salpingectomy or bilateral tubal ligation 3) Bilateral oophorectomy (4) For females with permanent infertility due to other medical reasons, eligibility will be determined by the investigator. 12. Female participants of childbearing potential must agree to use appropriate contraceptive measures from signing the informed consent form until 8 months after the last dose of study drug (refer to Appendix 12.10 of the protocol), and must not donate oocytes or breastfeed. Female participants intending to have children in the future must agree to undergo oocyte cryopreservation prior to initiation of study treatment. Male participants must agree to use barrier contraception from signing the informed consent form until 6 months after the last dose of study drug, and must not donate sperm. Male participants intending to have children in the future must agree to cryopreserve a sperm sample prior to initiation of study treatment.

1. Prior pathological diagnosis of mixed non-small cell lung cancer (e.g., combined small cell and non-small cell lung cancer, combined squamous cell carcinoma and adenocarcinoma) or any transformed non-small cell lung cancer (transformation from small cell lung cancer to non-small cell lung cancer). 2. Has received or is currently receiving any of the following therapies: (1) Prior or current use of B7-H3-targeted therapies, such as MGC018, DS-7300a, ABBV-155, BAT8009, Enoblituzumab, Omburtamab, etc.; (2) Prior or current use of topoisomerase I inhibitors, including antibody-drug conjugates bearing a topoisomerase I inhibitor payload, such as topotecan, irinotecan, trastuzumab deruxtecan, sacituzumab govitecan, Dato-Dxd (DS-1062), etc.; (3) Prior treatment with docetaxel alone or in combination with other agents; (4) Receipt of cytotoxic chemotherapy, investigational medicinal products, anticancer traditional Chinese medicines (see Appendix 12.1 for list), or other anticancer agents (including molecular targeted therapy or biologic therapy, etc.) within 2 weeks before randomization; (5) Receipt of macromolecular anticancer agents (including immunotherapy such as monoclonal antibodies and bispecific antibodies) within 4 weeks before randomization; (6) Receipt of local radiotherapy within 2 weeks before randomization; receipt of radiotherapy to more than 30% of bone marrow or extensive-field radiotherapy within 4 weeks before randomization; (7) Presence of pleural effusion/ascites requiring clinical intervention (patients with no need for drainage or stable effusion for >=1 week after drainage may be enrolled); presence of pericardial effusion (asymptomatic small-volume pericardial effusion not requiring clinical intervention per investigator assessment is permitted). If anticancer agents were administered locally (e.g., intrapleural infusion) at the time of drainage, a washout period of at least 5 drug half-lives or 21 days (whichever is shorter) before randomization. 3. Has persistent adverse reactions resulting from prior therapy that have not recovered to Grade 1 or baseline status before previous treatment, excluding alopecia, hearing loss, vitiligo, endocrine diseases stabilized by replacement therapy, and Grade 2 neuropathy; or such adverse reactions are deemed by the investigator, in agreement with the Sponsor, to have no clinical relevance to the participant's tolerance to the study intervention in the current clinical trial. 4. Untreated brain metastases; Uncontrolled brain metastases (except for asymptomatic metastases with no significant perilesional edema on imaging and no requirement for corticosteroid therapy for at least 2 weeks prior to the first dose); Presence of leptomeningeal metastases or brainstem metastases; Presence of spinal cord compression (detected by radiologic imaging, regardless of symptoms). 5. History of other primary malignant tumors, excluding: Radically cured solid tumors with no evidence of disease activity for >=5 years prior to study enrollment and extremely low risk of recurrence; adequately treated non-melanoma skin cancer or lentigo maligna with no evidence of disease recurrence; adequately treated carcinoma in situ (e.g., cervical carcinoma in situ) with no evidence of disease recurrence; non-metastatic prostate cancer with definitive treatment. 6. Has any of the following cardiac abnormalities: (1) Evidence of clinically significant cardiac arrhythmia or ECG abnormality (e.g., complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, PR interval > 250 ms); (2) Risk factors for QT interval prolongation or arrhythmic events, such as heart failure, refractory hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or concurrent use of any medication known to prolong the QT interval; (3) Mean Fridericia-corrected QT interval (QTcF) on resting ECG > 470 ms (Fridericia formula is provided in Appendix 12.3); (4) Left ventricular ejection fraction < 50%. 7. Has severe, uncontrolled or active cardiovascular and cerebrovascular diseases, including but not limited to: (1) Myocardial infarction within 6 months prior to randomization; (2) Unstable angina within 6 months prior to randomization that is not controlled by standard therapy; (3) Congestive heart failure (NYHA Class II or higher, NYHA Standards Committee, 1994) within 6 months prior to randomization; (4) Cerebrovascular accident (stroke) or transient ischemic attack within 6 months prior to randomization; (5) History of clinically significant atrial arrhythmia (as determined by the investigator) not controlled by standard therapy; (6) History of clinically significant ventricular arrhythmia (as determined by the investigator), or any clinically significant ventricular arrhythmia occurring during screening. 8. Has severe or poorly controlled hypertension, including but not limited to: history of hypertensive crisis or hypertensive encephalopathy; adjustment of antihypertensive medications within 2 weeks prior to randomization due to inadequate blood pressure control. Poorly controlled hypertension is defined as systolic blood pressure >= 180 mmHg or diastolic blood pressure >= 110 mmHg during screening. 9. Has severe or poorly controlled diabetes mellitus, including but not limited to: ① Diabetic ketoacidosis or hyperosmolar hyperglycemic state within 6 months prior to randomization; or ② other severe or poorly controlled diabetic conditions as judged by the investigator. 10. Has had a severe infection within 4 weeks prior to randomization, including but not limited to infectious complications requiring intravenous antibiotics for >= 2 weeks, bacteremia, severe pneumonia; has an active infection being treated with therapeutic intravenous antibiotics within 2 weeks prior to randomization. Participants receiving or having received prophylactic antibiotics (e.g., for urinary tract infection prophylaxis) are eligible for enrollment. 11. Has clinically significant bleeding symptoms or marked bleeding tendency within 1 month prior to randomization. 12. Has experienced a severe arterial or venous thromboembolic event (e.g., deep vein thrombosis, pulmonary embolism, etc.) within 3 months prior to randomization, excluding thrombosis related to implantable venous access ports, catheter-related thrombosis, or superficial vein thrombosis (these are not considered "severe" thromboembolic events). 13. Known or suspected history of interstitial pneumonia, immune pneumonitis, or radiation pneumonitis; presence or suspicion of interstitial pneumonia, immune pneumonitis, or radiation pneumonitis during screening; or moderate to severe pulmonary disease within 3 months prior to randomization that may interfere with the evaluation or management of drug-related pulmonary toxicity and severely impair respiratory function, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia/bronchiolitis obliterans, and moderate or severe ventilatory dysfunction on pulmonary function tests during screening. 14. Participants with active or history of potentially relapsing autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or patients at high risk (e.g., organ transplant recipients requiring immunosuppressive therapy). However, the following participants are eligible for enrollment: (1) Type 1 diabetes mellitus stabilized on fixed-dose insulin; (2) Autoimmune hypothyroidism requiring only hormone replacement therapy; (3) Skin diseases not requiring systemic therapy (e.g., eczema, rash involving < 10% of body surface area, psoriasis without ocular manifestations, etc.). Asthma requiring medical intervention with bronchodilators is not eligible for enrollment. 15. History of severe or life-threatening immune-mediated adverse events (including adverse events leading to permanent discontinuation of immunotherapy). 16. Has any of the following conditions: (1) Body mass index (BMI) < 18.0 kg/m^2 within 2 months prior to the first dose, or weight loss >= 10% within 2 months prior to the first dose. (2) Severe malnutrition with current intravenous hyperalimentation, or requirement for hospitalization and continuous intravenous infusion therapy. Patients may be enrolled if their nutritional status has been effectively controlled and stable for more than 28 days prior to randomization. 17. Has current hepatic encephalopathy, hepatorenal syndrome, or cirrhosis of Child-Pugh Grade B or higher. 18. Has any active renal disease (e.g., infection, requirement for dialysis, or any other renal disease that may compromise participant safety). Note: Renal obstruction successfully managed with stenting is permitted. 19. Has received continuous glucocorticoid therapy for more than 30 days within 30 days prior to randomization, or requires long-term (>=30 days) glucocorticoid therapy (excluding patients on topical corticosteroids for skin disorders and those receiving low-dose corticosteroids as replacement therapy for adrenal insufficiency), or has other acquired or congenital immunodeficiency diseases, or a history of organ transplantation (excluding corneal transplantation). Use of systemic glucocorticoids at physiological replacement doses (<=10 mg/day prednisone or equivalent) is permitted. 20. Has undergone any major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose. Major surgery is defined as Grade 3 and Grade 4 procedures as specified in the Measures for the Administration of Clinical Application of Medical Technologies. 21. Individuals with a history of severe allergies (e.g., anaphylactic shock), or who have experienced severe infusion reactions, or who are allergic to recombinant human or murine proteins are prohibited from participating in this study. Known hypersensitivity to any component or excipient of the investigational products (HS-20093, adebrelimab, docetaxel, or other formulations containing polysorbate 80) also precludes study participation. 22. Has received any live attenuated vaccine within 30 days prior to randomization. COVID-19 vaccines authorized through appropriate regulatory mechanisms (e.g., emergency use authorization, conditional marketing authorization, or license application) are not excluded. Note: mRNA and adenovirus-based COVID-19 vaccines are considered non-live vaccines. 23. Is currently enrolling in or participating in any other clinical trial involving investigational interventions or other interventional medical studies. Participation in the follow-up phase of studies without administration of investigational products, non-interventional registry studies, or epidemiological studies is permitted. 24. Has any severe and/or unstable medical or psychiatric disorder, or other conditions (including abnormal laboratory findings) that may interfere with the provision of informed consent, compliance with study procedures, interpretation of study outcomes, or may expose participants to significant safety risks associated with study drug administration.

In this trial, participants were randomized using an Interactive Web Response System (IWRS). The randomization method was stratified block randomization. Stratification factors included: 1. Baseline brain metastasis at enrollment (present; absent) 2. Baseline ECOG PS score (0; 1) 3. Baseline tumor PD-L1 expression (TPS < 1%; TPS >= 1%) Participants were randomized in a 1:1 ratio to either the experimental group (HS-20093 plus adebrelimab) or the control group (docetaxel). If a participant withdrew from the study, the randomization number assigned by the IWRS.

Open-label study

No sharing of raw data

1. Case Report Form (CRF)；2. Electronic Data Capture and Management System (EDC)