Advanced or metastatic non-squamous non-small cell lung cancer
Conditions
Interventions
control group:docetaxel therapy
experimental group:HS-20093 in combination with adebrelimab
Sponsors
Hunan Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 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 t
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1;OS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Exploratory endpoints: Relationship between exposure metrics and clinical endpoints (efficacy and safety);Incidence and severity of AEs and SAEs;Exploratory endpoint: Proportion of patients positive for anti-HS-20093 antibodies and anti-adebrelimab antibodies (ADA);Exploratory endpoint: Exploration of the correlations between expression levels of B7-H3 and programmed cell death ligand 1 (PD-L1), sB7-H3 concentration levels, and efficacy.;Exploratory endpoint: Pharmacokinetic (PK) profiles of HS-20093 and adebrelimab, including peak concentration (Cmax), time to peak concentration (Tmax), area under the plasma concentration-time curve;Objective response rate (ORR), disease control rate (DCR), and duration of response (DoR) assessed by BICR per RECIST v1.1;ORR, DCR, DoR and PFS assessed by the investigator per RECIST v1.1;Changes from baseline in vital signs, laboratory tests (complete blood count and blood biochemistry), cardiac function [electrocardiogram (ECG)], and Eastern Cooperative Oncology Group (ECOG) performa; | — |
Countries
China
Contacts
Public ContactLin Wu
Hunan Cancer Hospital
Outcome results
None listed