A Phase Ib/II Study Evaluating Injectable ALK-N001 in Patients With Advanced Solid Tumors

Exclusion Criteria

• •1\. Have received anti-tumor therapies such as chemotherapy, radiotherapy (local bone radiotherapy within 2 weeks), biological therapy, macromolecular targeted therapy, immunotherapy, or TIL cell therapy within 4 weeks prior to the first dose of the study drug, including the following: Have received anti-cancer endocrine therapy (excluding GnRH agonists or inhibitors, endocrine replacement therapy or contraceptives), oral fluoropyrimidines, small-molecule targeted drugs as well as traditional Chinese medicines with anti-tumor indications within 2 weeks or 5 half-lives prior to the first dose of the study drug (whichever is longer); Have received CAR-T, CAR-NK cell therapy or tumor vaccine therapy within 3 months prior to the use of the study drug; Have received inactivated viral vaccine injection within 2 weeks prior to the use of the study drug, or non-inactivated viral vaccine injection within 4 weeks prior to the use of the study drug; Have received other unlisted clinical trial drugs within 4 weeks or 5 half-lives prior to the use of the study drug (whichever is shorter);
• •2\. Have used CYP3A4 strong inducers or strong inhibitors within 7 days prior to the first dose or need to use them during the study;
• •3\. Have previously used DXD analogues, irinotecan and other drugs;
• •4\. Have a known history of severe allergic reactions (NCI-CTCAE v6.0 grade ≥3) to the components of the preparations used in the trial;
• •5\. Have central nervous system (CNS) metastases and/or leptomeningeal metastases; Study participants with treated brain metastases are allowed to participate in this study if the brain metastatic lesions have been stable for at least 1 month, there is no evidence of new or enlarged brain metastases, and steroid therapy has been discontinued for 2 weeks before the first dose;
• •6\. Have other malignant tumors within 5 years before enrollment; Exceptions include cured carcinoma in situ of cervix, cutaneous squamous cell carcinoma, basal cell carcinoma or papillary thyroid carcinoma;
• •7\. Have clinically uncontrolled third-space effusions that are deemed unsuitable for enrollment by the investigator;
• •8\. Have pre-existing severe digestive diseases such as chronic inflammatory bowel disease and/or intestinal obstruction or chronic diarrhea;
• •9\. Have severe cardiovascular diseases, including but not limited to: a) Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, second to third-degree atrioventricular block, etc.; b) Acute coronary syndrome, congestive heart failure, stroke or other grade 3 and above cardiovascular events within 6 months before the first dose; c) New York Heart Association (NYHA) functional classification ≥ grade II or left ventricular ejection fraction (LVEF) \<50%, or other structural heart diseases judged to be high-risk by the investigator; d) ECG examination showing QTcF \>450ms (male), \>470ms (female) (according to Fridericia formula: QTcF=QT/(RR\^0.33)), (Note: If the initial examination is abnormal, re-measure twice within 48 hours and take the average of three measurements to judge eligibility); e) Clinically uncontrolled hypertension (systolic blood pressure ≥150mmHg and/or diastolic blood pressure ≥100mmHg after intervention); f) Poorly controlled diabetic patients defined as glycated hemoglobin (HbA1c) ≥8.0%;
• •10\. Currently have active infections and have received systemic anti-infective treatment within 2 weeks before the first dose (excluding biopsy and prophylactic use for urinary tract surgery);
• •11\. Have active hepatitis B during screening (HBsAg positive and HBV-DNA \>500IU/ml or the lower limit of detection of the study center \[only when the lower limit of detection of the study center is higher than 500IU/ml\]), active hepatitis C (patients with positive HCV antibodies but HCV-RNA \< the lower limit of detection of the study center are allowed to be enrolled); Patients receiving preventive antiviral treatment other than interferon are allowed to be enrolled; Patients with positive screening results for active syphilis or human immunodeficiency virus (HIV);
• •12\. Have severe pulmonary diseases such as pulmonary embolism and interstitial lung disease within 6 months before the first dose;
• •13\. Have a history of deep vein thrombosis or any other severe thromboembolism within 6 months before the first dose (implantable venous access port or catheter-related thrombosis, superficial venous thrombosis or lacunar infarction are not regarded as "severe" thromboembolism); Known familial and/or acquired thrombophilia, such as hereditary or acquired defects in anticoagulant proteins, coagulation factors, fibrinolytic proteins, or high thromboembolic risk due to acquired risk factors;
• •14\. Have active hemorrhagic diseases or other grade ≥3 hemorrhage history within 4 weeks before the first dose; High bleeding risk caused by obvious invasion of large arteries by tumor metastases;