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

An Open-label, Multicenter Phase Ib/II Study Evaluating the Efficacy, Safety and Pharmacokinetics of Injectable ALK-N001 in Patients With Advanced Solid Tumors

This study is a multicenter, open-label, dose-escalation and cohort-expansion Phase Ib/II clinical trial conducted in patients with advanced solid tumors, aiming to evaluate the safety, pharmacokinetics and efficacy of ALK-N001 for injection as monotherapy in the treatment of advanced solid tumors.

Inclusion Criteria:

• 1. Voluntarily signs the informed consent form, understands the study, and is willing and able to comply with all study procedures.
• 2. Male or female aged 18 years or older.
• 3. Has histologically and/or cytologically confirmed unresectable and/or metastatic advanced solid tumor.
• 4. Dose Expansion Phase (Phase Ib): Patients with advanced solid tumors who have failed standard treatment, currently have no standard treatment available, or are intolerant to standard treatment, including but not limited to lung cancer, pancreatic cancer, esophageal cancer, liver cancer, breast cancer (triple-negative breast cancer or HER2 low/ultra-low expression breast cancer), ovarian cancer, cervical cancer, and other tumor types.
• 5.Dose Expansion Phase (Phase II): Including but not limited to the following 4 cohorts: ① Lung Cancer Cohort (small cell lung cancer, non-squamous non-small cell lung cancer, squamous cell lung cancer): Failed at least one line of standard treatment; ② Breast Cancer Cohort (triple-negative breast cancer or HER2 low/ultra-low expression breast cancer): Failed at least one line of standard treatment; ③ Ovarian Cancer, Cervical Cancer, Pancreatic Cancer, and Liver Cancer Cohort: Failed at least one line of standard treatment; ④ Esophageal Cancer Cohort: Failed at least one line of standard treatment. There is documentation confirming radiologically confirmed disease progression after the last anti-tumor treatment. If a specific tumor type shows clear anti-tumor activity signals (e.g., meeting the preset efficacy threshold) during the Phase Ib study, the sponsor may initiate an additional dose expansion cohort for the effective tumor type during or after the Phase II study, to further verify its efficacy and safety.
• 6.According to RECIST Version 1.1, there is at least one measurable tumor lesion. (Tumor lesions located in previously irradiated areas or other locally treated sites are generally not considered measurable, unless there is clear evidence of progression of the lesion.)
• 7.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 8. Expected survival time of ≥ 3 months.
• 9.Adequate organ function as follows: hematologic system (no blood transfusion or hematopoietic growth factor within 14 days): absolute neutrophil count ≥1.5×10⁹/L, platelets ≥90×10⁹/L, hemoglobin ≥90 g/L; liver function: total bilirubin ≤1.5×ULN, alanine aminotransferase ≤3×ULN (≤5×ULN in patients with liver metastasis or liver cancer), aspartate aminotransferase ≤3×ULN (≤5×ULN in patients with liver metastasis or liver cancer); renal function: creatinine ≤1.5×ULN, creatinine clearance ≥50 mL/min calculated by Cockcroft-Gault formula (required only if creatinine >1.5×ULN); coagulation function: activated partial thromboplastin time ≤1.5×ULN, international normalized ratio ≤1.5×ULN.
• 10. Male subjects and females of childbearing potential must agree to use non-pharmacological contraceptive measures from signing informed consent until 6 months after the last dose.

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;
• 15. Toxic reactions from previous anti-tumor treatments have not recovered to ≤ grade 1 (severity assessed according to NCI-CTCAE v6.0, excluding alopecia and other toxicities judged to have no safety risks by the investigator) or the level specified in the inclusion criteria;
• 16. Currently receiving thrombolytic or anticoagulant therapy (excluding prophylactic anticoagulant therapy);
• 17. Have received allogeneic hematopoietic stem cell transplantation or organ transplantation;
• 18. Have a history of mental disorders (including epilepsy or dementia, etc.);
• 19. Study participants have a history of drug abuse, or have medical, psychological or social conditions that may interfere with study participation or evaluation of study results;
• 20. Female study participants who are breastfeeding or have positive blood/urine pregnancy results during the screening period;
• 21. Any other conditions of the study participant (such as psychological, geographical or medical conditions) that do not allow them to comply with the study and follow-up procedures, or other circumstances where the study participant is deemed unsuitable for enrollment in this study by the investigator.