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This study compares the drug IBI363 with Docetaxel in patients with advanced squamous (non-small cell) lung cancer after standard treatments have failed. Adults aged 18 and older with measurable disease that is resistant to, or has progressed after, platinum-based chemotherapy and anti-PD-1/PD-L1 therapy may take part. The study is in Phase 3 and is currently recruiting participants.
The summary above is a plain-language rendering of the official record. The original English title is shown for reference.
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Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.
Inclusion Criteria:
1. Willing to sign the written informed consent form and be able to comply with the visit schedule and related procedures specified in the protocol.
2. Male or female participants must be at least 18 years old or the legal age of majority in their country, whichever is greater.
3. Have locally unresectable advanced or metastatic histologically or cytologically confirmed squamous NSCLC Note: Mixed small cell carcinoma, or other pathological components are excluded.
4. Resistant or refractory to systemic anti-tumor therapy, including platinum-based doublet chemotherapy and primary or secondary resistance to anti-PD-1/PD-L1 monoclonal antibody given in combination or sequentially; or given as neoadjuvant and/or adjuvant therapy, which will be considered first-line treatment if the disease has recurred or progressed during such treatment or within 6 months after discontinuation.
5. Radiographic progression per RECIST v1.1 during or within 6 months after discontinuation of anti-PD-1/PD-L1 monoclonal antibody treatment.
6. Agree to provide archival (collected within 2 years before signing the informed consent form if biopsy cannot be performed or participant refuses fresh biopsy) tumor tissue specimens for PD-L1 expression level testing and exploratory analysis of other biomarkers.
7. Have at least one measurable lesion (target lesion) by computed tomography (CT) or magnetic resonance imaging (MRI) according to RECIST v1.1. Lesions that have previously received radiotherapy or intratumoral injection can be used as measurable lesions if they show progression after treatment (either tissue confirmed or more than 3 months after treatment) as per RECIST v1.1.
8. ECOG PS score of 0 or 1.
9. Expected survival time ≥ 3 months.
10. Women of childbearing potential (WOCBP) or men with female partners of childbearing potential must agree to take effective contraceptive measures during the entire course of treatment and for 6 months after the last dose of study treatment.
11. Lactating women must agree to strictly abstain from breastfeeding during the entire Treatment Period and for 6 months after the treatment.
Exclusion Criteria:
1. Women who are pregnant or lactating, or intending to become pregnant before, during, or within 6 months after the last dose of any study drug. WOCBP or fertile men with WOCBP partner(s), not using and/or not willing to use a highly effective method of contraception.
2. Known actionable genomic alteration, including any of the following driver gene mutations:
* Epidermal growth factor receptor (EGFR): including exon 19 deletion, exon 21 L858R, exon 20 T790M, exon 20 S768I, exon 21 L861Q, exon 18 G719X, and exon 20 insertion mutations.
* Kirsten rate sarcoma virus (KRAS) G12C mutation.
* Anaplastic lymphoma kinase (ALK) rearrangement.
* ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) rearrangement.
* B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation.
* Neurotrophic tyrosine receptor kinase (NTRK) 1/2/3 fusion.
* MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 skipping mutation.
* RET proto-oncogene (RET) rearrangement.
* V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2, also known as HER2) mutation.
* Other gene mutation types where a targeted therapy has been completely approved for marketing by a local regulatory authority.
Note: It is not mandatory to have undergone driver gene testing.
3. Active or symptomatic brain metastases. Participants who are clinically and radiologically stable at least 4 weeks after treatment and participants with small, asymptomatic, incidental, untreated brain metastases that remain stable ≥ 4 weeks may participate in this study as long as they meet all of the following criteria:
* No metastases to meninges, midbrain, pons, medulla oblongata, spinal cord or cerebellar metastases.
* No compression of the aqueduct of Sylvius, no compression of the third or fourth ventricle, no compression of the spinal cord.
* Total diameter of metastases ≤ 2 cm and total number of metastases ≤ 3.
* After the completion of treatment for brain metastases, repeated imaging examination confirming no evidence of new brain metastases or enlargement of the original brain metastases must be ≥ 4 weeks from completion of radiotherapy (stereotactic radiosurgery or whole brain irradiation) using same imaging technique; no steroids, anticonvulsant, or dehydration (such as mannitol) therapy is required, and the symptoms are stable ≥ 14 days prior to randomization.
* Measurable lesions per RECIST 1.1 excluding brain metastases.
4. Presence of any of the following hematologic abnormalities at Baseline\*:
* Hemoglobin \< 9 g/dL.
* Absolute neutrophil count (ANC) \< 1,500 per mm3.
* Platelet count \<100 x 103/mm3. \*""Baseline"" is defined as the last available observation prior to the first dose of investigational medical product. Note: Participants must not receive supportive treatments such as blood products (including red blood cell suspension, apheresis platelets, cryoprecipitation, etc.), erythropoietin, or colony-stimulating factors within 7 days prior to blood sampling.
5. Presence of any of the following serum chemistry abnormalities at Baseline:
* Total bilirubin \> 1.5 × upper limit of normal (ULN) except for participants with Gilbert's syndrome with serum bilirubin ≤ 3 × ULN or if concurrent conjugated bilirubin ≤ ULN.
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 × ULN; for liver metastasis, AST or ALT \> 5.0 × ULN.
* Creatinine Clearance (CrCl) \< 30 mL/min; the Cockcroft-Gault formula is used to calculate CrCl (using ideal body weight for obese participants and actual body weight for non-obese participants).
* Albumin \< 30 g/L. Note: Investigators should refer to the local clinical practice guidelines or the label of docetaxel to assess whether participants with abnormal serum chemistry are suitable for docetaxel treatment.
6. Presence of any of the following coagulation parameter abnormalities at Baseline:
* International normalized ratio (INR) \> 1.5 × ULN (\> 3 × ULN if on stable dose anticoagulation).
* Partial thromboplastin time (PTT; or activated partial thromboplastin time \[aPTT\]) \> 1.5 × ULN (\> 3 × ULN if on stable-dose anticoagulation).
7. History of deep venous thrombosis, pulmonary embolism, or any other serious thromboembolic events within 3 months prior to enrollment (implantable port or catheter-related thrombosis, or superficial venous thrombosis are not considered ""serious"" thromboembolisms); portal vein tumor thrombus involving both the main trunk and bilateral first-order branches, or involving both the main trunk and superior mesenteric vein, or inferior vena cava tumor thrombus.
8. Active uncontrolled bleeding or known bleeding tendency. For example, imaging shows that the tumor invades large blood vessels or has unclear boundaries (including aorta, pulmonary aorta, left pulmonary artery, right pulmonary artery, pulmonary vein, superior vena cava, inferior vena cava, etc.), or the investigator judges that the tumor is very likely to invade important blood vessels and cause fatal bleeding during the subsequent study.
9. Presence of clinically significant cardiovascular or cerebrovascular diseases, including:
* Symptomatic, clinically unstable arrhythmia or arrhythmia requiring clinical intervention.
* Severe conduction disorders (such as third-degree atrioventricular block and bundle branch block).
* QT interval corrected for heart rate (QTc interval, calculated using Fridericia's formula) ≥ 480 ms.
* Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg) despite standard treatment.
* History of myocarditis.
* Left ventricular ejection fraction (LVEF) \< 50%.
* Congestive heart failure requiring treatment.
* Class II-IV cardiac insufficiency according to the New York Heart Association (NYHA) functional classification.
* History of acute coronary syndrome (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to the first dose of investigational medical product.
* Cerebrovascular accident or transient ischemic attack within 6 months before the first dose of the investigational medical product.
* History of seizures.
10. Cardiac enzymes ≥ levels consistent with myocardial infarction as defined by the manufacturer (i.e., Grade 3).
11. History of the following lung diseases requiring steroid therapy: interstitial lung disease (ILD), pulmonary fibrosis, drug-related and radiation pneumonitis; current active pulmonary infection requiring anti-infective therapy; active pulmonary tuberculosis within 1 year prior to enrollment; severely impaired pulmonary function, including but not limited to the following: pulmonary embolism, severe asthma or chronic obstructive pulmonary disease within 3 months prior to randomization; autoimmune, connective tissue, or inflammatory diseases involving the lungs (such as rheumatoid arthritis, Sjögren's disease, and sarcoidosis); previous unilateral pneumonectomy.
12. History of severe, poorly controlled allergies, asthma or atopic dermatitis (except for atopic dermatitis caused by immunotherapy). Note: remote history of childhood asthma is not exclusionary.
13. History of anaphylactic or hypersensitivity reactions. Uncontrolled third space effusion requiring repeated drainage, such as pleural effusion, abdominal effusion, pericardial effusion, etc.
Note: Participants with the following conditions may be enrolled:
* No need for drainage.
* No significant increase in effusion after stopping drainage determined using at least 2 ultrasound examinations (at least 7 days apart).
14. Current or recent (within 6 months) significant gastrointestinal disease or condition, including:
* Flare of inflammatory bowel disease.
* Grade ≥ 2 diarrhea (CTCAE v5.0) within 2 weeks prior to the first dose of the investigational medical product.
15. Active autoimmune disease requiring systemic treatment (e.g., use of disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years before the first dose.
Note: Replacement therapies (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatments and exclusionary.
16. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
17. Known or suspected allergy to the investigational medical product and any excipients. Known or suspected severe hypersensitivity reactions to docetaxel or to drugs formulated with polysorbate 80.
18. Prior history of significant toxicity related to immune checkpoint inhibitor administration that required permanent discontinuation of this therapy.
19. Unresolved Grade \> 1 toxicity related to any previous anti-tumor therapy (excluding alopecia, asthenia, hypothyroidism requiring only thyroid hormone replacement therapy, hyperglycemia requiring only insulin replacement therapy, adrenal insufficiency requiring physiological steroid replacement, electrolyte abnormalities requiring only symptomatic treatment, and other conditions not affecting the investigational medical product treatment as assessed by the investigator).
20. Have not adequately recovered from previous surgery or have undergone any major surgery, such as carotid artery stenting or esophageal stenting, within 4 weeks before the first dose of investigational medical product.
21. Uncontrolled tumor-related pain or symptomatic hypercalcemia.
22. Uncontrolled human immunodeficiency virus (HIV), active syphilis, active hepatitis B (HBV), hepatitis C (HCV), or tuberculosis.
* Participants who are HIV-positive must have CD4 ≥ 350 cells/µL. Participants on established HAART (assuming no expected drug-drug interactions) for at least 4 weeks must an HIV viral load \< 400 copies/mL.
* Participants with positive results of Treponema pallidum haemagglutination (TPHA)/Treponema pallidum particle agglutination (TPPA) test and/or rapid plasma regain test (RPR) should not be enrolled.
* Participants with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) should undergo hepatitis B virus (HBV) DNA testing. If the HBV DNA copy number is ≤ 2.5 × 103 copies/mL or ≤ 500 IU/mL or below the lower limit of detection, the participant can be enrolled. Participants who are HBsAg (+) should receive anti-HBV treatment throughout the Treatment Period to avoid viral activation. For participants with anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), prophylactic anti-HBV treatment can be considered but is not required; however, close monitoring for viral reactivation is required.
* Participants with positive HCV serology results but negative or below the lower limit of detection of HCV RNA can be included in the study.
* Participants who received HCV treatment and have undetectable viral load results are allowed.
* Participants with previously cured or clinically stable remote history of tuberculosis as assessed by the investigator can be included in the study.
23. Serious/active/uncontrolled infection, infection requiring systemic intravenous antibiotics, or fever of unknown origin (≥ 38°C) within 2 weeks before the first dose of investigational medical product(s).
24. History or current evidence of any disease, treatment, or laboratory abnormality that, in the judgment of the investigator, could compromise the safety of the participant, interfere with obtaining informed consent, affect participant compliance, or affect safety evaluations of the investigational medical product.
25. Psychiatric illness, altered mental status, or drug abuse that prevents understanding of the informed consent process and/or completion of required study-related evaluations.
26. Unable to meet protocol requirements for known or foreseeable reasons per investigator judgement.
27. Diagnosed with other pathologically confirmed malignancies within 5 years prior to informed consent, with the exception of radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ, localized prostate cancer, papillary thyroid cancer, and other radically treated malignancies with no known active disease for at least 2 years prior to enrollment and with a very low risk of recurrence.
28. Received any of the following excluded medications or treatments:
* Docetaxel.
* Received more than one anti-PD-1/PD-L1 monoclonal antibody therapy.
* Systemic anti-tumor therapy except anti-PD-1/PD-L1 monoclonal antibody and platinum-based doublet chemotherapy including but not limited to bispecific antibodies, targeted therapy, antibody drug conjugate, other immune checkpoint inhibitors.
* IL-2/IL-15 cytokine.
* Chemotherapy within 2 weeks or 5 half-lives (whichever is longer) before the first dose of investigational medical product without delayed toxicity.
* Anti-tumor antibody therapy (excluding antibody drugs such as denosumab for the treatment of bone metastases) within 4 weeks before the first dose of the investigational medical product.
* Palliative radiotherapy within 2 weeks prior to the first dose of investigational medical product.
* Live vaccine within 28 days prior to the first dose of investigational medical product.
* Immunosuppressive or systemic steroid therapy (\> 10 mg/day of prednisone or equivalent) within 2 weeks prior to the first dose of investigational medical product.
* Received traditional Chinese medicine with anti-tumor indications within 1 week before the first dose of the investigational medical product.