A clinical trial of QLC5508 for advanced solid tumors

The goal of this clinical trial is to learn if QLC5508 can be given safely to adults with advanced solid tumors. It will also learn how two different formulations of QLC5508 compare in the body, and whether other drugs affect QLC5508. The main questions it aims to answer are:

Does a single injection of QLC5508 change the heart's electrical activity (QTc interval)?

How do the test formulation and the reference formulation of QLC5508 compare in the body (pharmacokinetics)?

Do other drugs (itraconazole, darolutamide, or rifampicin) change how the body processes QLC5508?

Investigators will compare the test formulation to the reference formulation, and will also give QLC5508 together with itraconazole, darolutamide, or rifampicin to look for drug-drug interactions.

Participants will:

Receive QLC5508 by injection into a vein;

Join one of three groups: two groups will receive both formulations of QLC5508 at different times (crossover) and also take rifampicin or itraconazole; the third group will take darolutamide with QLC5508;

Have heart monitoring (Holter) during the first dose;

Undergo regular blood tests, safety checks, and immunogenicity testing (to see if the body develops antibodies against QLC5508).

Inclusion Criteria:

• Participants must voluntarily sign the Informed Consent Form (ICF) and demonstrate the capacity to understand and adhere to study requirements.

• Participants must be ≥18 years of age at the time of signing the ICF, regardless of sex.

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1 (refer to Appendix 2).

• Life expectancy of ≥6 months.

• Histologically or cytologically confirmed advanced malignant solid tumor, with failure of, intolerance to, or absence of standard therapy.

• According to RECIST v1.1, participants must have at least one measurable lesion; participants with non-target lesions only are allowed.

• Adequate organ function within 7 days prior to the first dose of the investigational product. (Note: Use of any blood products, cell growth factors, leukocyte/platelet-boosting agents, anemia-correcting drugs, or hepatoprotective treatments is strictly prohibited during this 7-day screening window.):

  1. Hematology: Absolute neutrophil count ≥1.5 × 10⁹/L; Platelet count ≥100 × 10⁹/L; Hemoglobin ≥90 g/L.
  2. Renal function: Serum creatinine ≤1.5 × Upper Limit of Normal (ULN); for participants with creatinine >1.5 × ULN, Creatinine Clearance (CrCl) calculated via the Cockcroft-Gault formula must be ≥60 mL/min.
  3. Hepatic function: Total bilirubin ≤1.5 × ULN (≤3 × ULN permitted for participants with Gilbert's syndrome; ≤2.5 × ULN permitted for those with liver metastases). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤5 × ULN permitted for participants with Gilbert's syndrome or liver metastases). Albumin (ALB) ≥25 g/L.
  4. Coagulation: International Normalized Ratio (INR) or Activated Partial Thromboplastin Time (APTT) ≤1.5 × ULN.

• Left Ventricular Ejection Fraction (LVEF) ≥50%.

• Recovery from all reversible Adverse Events (AEs) related to prior anti-tumor therapy to ≤Grade 1 (per NCI-CTCAE v6.0), excluding alopecia (any grade) and ≤Grade 2 peripheral neuropathy. Participants with other abnormal findings deemed clinically insignificant or at no safety risk by the Investigator are eligible.

• Participants of childbearing potential (both female and non-sterilized male) must agree to use reliable contraceptive methods from the time of signing the ICF until at least 180 days after the last dose of the investigational product (refer to Appendix 3). Sperm or ova donation must be avoided during this period.

• Female participants of childbearing potential must be non-lactating and have a negative serum pregnancy test within 7 days prior to the first dose.

Exclusion Criteria:

• Received chemotherapy, biotherapy, immunotherapy, antibodies, ADCs, or other anti-tumor therapies within 4 weeks prior to the first dose of the investigational product. Special circumstances are as follows:

  1. Includes oral fluoropyrimidines, small molecule targeted drugs, endocrine therapy, palliative radiotherapy, or traditional Chinese medicine (TCM) treatments with anti-tumor indications within 2 weeks prior to the first dose;
  2. Includes mitomycin or nitrosourea-based drugs within 6 weeks prior to the first dose;
  3. Includes cell-based therapies or anti-tumor vaccines within 8 weeks prior to the first dose;

• Presence of uncontrolled or symptomatic Central Nervous System (CNS) metastases, leptomeningeal metastases, or spinal cord compression due to metastasis prior to signing the ICF. The following exception applies: Participants with symptomatic CNS metastases who received treatment and have achieved radiological stability for ≥4 weeks (defined as two brain images acquired using the same imaging modality, both collected after CNS metastasis treatment and at least 4 weeks apart, showing no evidence of intracranial progression upon comparison), exhibit no signs of cerebral edema, and have discontinued systemic corticosteroid treatment (at any dose) for >2 weeks prior to the first dose of the investigational product;

• History of other active malignancies within 3 years prior to signing the ICF, except for the following: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, prostatic carcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, or other malignancies that have been treated, show no evidence of disease for >2 years, and do not require ongoing treatment;

• Within 1 week prior to the first dose or within 5 half-lives of using the following drugs (whichever is longer), received strong or moderate inhibitors or inducers of CYP3A, P-glycoprotein (P-gp), Breast Cancer Resistance Protein (BCRP), or Organic Anion Transporting Polypeptide (OATP1B1); or participants requiring continued treatment with these drugs during the study period in Cycles C1 and C2 (list of drugs provided in Appendix 5);

• Human Immunodeficiency Virus (HIV) positive participants; positive Treponema pallidum antibodies (participants with a negative titer test are allowed); positive Hepatitis B Surface Antigen (HBsAg) with Hepatitis B virus Deoxyribonucleic acid (HBV-DNA) ≥2000 IU/mL or 10⁴ copies/mL; positive Hepatitis C virus (HCV) antibodies with positive Hepatitis C virus Ribonucleic acid (HCV-RNA) (Note: If HCV-RNA cannot be tested at the study site, results from a qualified tertiary hospital are acceptable);

• Within 6 months prior to signing the ICF, history of comorbid cardiovascular or cerebrovascular diseases, including but not limited to:

Myocardial infarction, severe/unstable angina, stroke or transient ischemic attack, myocarditis, congenital heart diseases such as clinically significant valvular stenosis, regurgitation, and cardiomyopathy; Severe or uncontrolled hypertension, including: history of hypertensive crisis or hypertensive encephalopathy; persistent systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg after optimal treatment; Cardiac insufficiency classified above Class II according to the New York Heart Association (NYHA) Functional Classification, as well as participants with clinically significant supraventricular or ventricular arrhythmias; Participants with a mean corrected QT interval (QTcF) >450 ms (males) or >470 ms (females) on the 12-lead electrocardiogram prior to the first dose of the investigational product; Presence of any factors that increase the risk of QTc prolongation or arrhythmic events, such as refractory hypokalemia, congenital long QT syndrome, family history of long QT syndrome, unexplained sudden death in immediate family members under 40 years of age, or concomitant medications that prolong the QT interval (receiving or requiring continued treatment with these medications during the study period);

• Occurrence of severe arterial or venous thromboembolic events within 3 months prior to the first dose, such as deep vein thrombosis, pulmonary embolism, etc. (Implantable venous access port-related, catheter-induced thrombosis, or superficial venous thrombosis are excluded and not considered "severe" thromboembolism);
• Received systemic corticosteroids (prednisone >10 mg/day or equivalent doses of similar drugs) or other immunosuppressants such as cyclophosphamide, azathioprine, methotrexate, and anti-TNF-α agents within 14 days prior to the first dose; the following exceptions apply: use of topical, ophthalmic, intra-articular, nasal, or inhaled corticosteroids; short-term use of corticosteroids for prophylactic treatment (e.g., prevention of contrast agent allergy);
• Participated in any other clinical research study and used other investigational products (excluding minerals, vitamins, etc.) within 4 weeks (or unknown half-life) prior to the first dose, or less than 2 weeks (half-life ≤3 days) or less than 28 days (half-life >3 days) from the last dose of the previous investigational product;
• Known allergy to any components of QLC5508, Itraconazole capsules, Rifampicin capsules, or Darolutamide tablets, or their excipients; history of severe allergy (such as anaphylactic shock), severe infusion reaction, or allergy to recombinant human or murine protein substances;
• Presence of other severe physical or psychiatric illnesses, or abnormal laboratory tests that may increase the risk of participating in the study or interfere with the study results, and participants deemed unsuitable for participation by the Investigator.