A Clinical Trial Evaluating TQB2101 in Subjects With Advanced Hematologic Malignancies

A Phase I Clinical Trial Evaluating the Safety and Efficacy of TQB2101 in Subjects With Advanced Hematologic Malignancies

TQB2101 for Injection is an Antibody-Drug Conjugate (ADC) targeting Receptor Tyrosine Kinase Like Orphan Receptor 1 (ROR1).It consists of three main components: a ROR1 monoclonal antibody responsible for selectively recognizing the surface antigen of cancer cells, a small molecule toxin responsible for killing cancer cells, and a linker connecting the antibody and the small molecule toxin. It is intended for clinical use in the treatment of advanced malignant tumors, including advanced malignant hematological tumors.

Inclusion Criteria:

• Subjects voluntarily participate in this study, sign the informed consent form, and demonstrate good compliance.

• Age between 18 and 75 years (calculated based on the date of signing the informed consent form).

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.

• Expected survival >12 weeks.

• Subjects with advanced hematologic malignancies confirmed by cytology/histopathology, who have failed standard treatment or lack effective treatment options.

• At least one measurable lesion according to the 2014 Lugano criteria: lymph node lesions with long axis >15mm or extranodal lesions with long axis >10mm on CT cross-sectional imaging.

• Adequate organ function meeting the following criteria:

  1. Hemoglobin (HGB) ≥80g/L
  2. Absolute neutrophil count (ANC) ≥1.0×10⁹/L
  3. Platelet count (PLT) ≥75×10⁹/L (≥50×10⁹/L if with bone marrow involvement)
  4. Total bilirubin (TBIL) ≤1.5×ULN
  5. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤2.5×ULN (≤5×ULN if with liver metastases)
  6. Serum creatinine (CR) ≤1.5×ULN OR creatinine clearance rate (CCR) ≥60ml/min (calculated using standard Cockcroft-Gault formula)
  7. Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), and International Normalized Ratio (INR) ≤1.5×ULN (without anticoagulation therapy)

• Women of childbearing potential must agree to use effective contraception during the study and for 6 months after study completion, with negative blood pregnancy test within 7 days prior to enrollment; male subjects must agree to use effective contraception during the study and for 6 months after study completion.

Exclusion Criteria:

• Patients with other malignant tumors that occurred within 3 years before the first administration or currently coexisting with other malignant tumors are excluded, except for those who have undergone a single surgical treatment for other malignant tumors and have achieved a disease-free survival (DFS) of 5 consecutive years; patients with cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading the basement membrane)] are eligible for inclusion.

• Tumor-related symptoms and treatments:

  1. Lymphoma involving or suspected to involve the central nervous system, or primary central nervous system lymphoma;
  2. Patients who have received chemotherapy, immunotherapy within 4 weeks before the first administration, radiotherapy or small molecule targeted drugs within 2 weeks, or are still within 5 half-lives of the drug (whichever occurs earlier), with a washout period calculated from the end of the last treatment;
  3. Patients who have received treatment with traditional Chinese medicine with clear anti-tumor indications in the National Medical Products Administration (NMPA) approved drug instructions (including Compound Cantharidin Capsules, Kang'ai Injection, Kanglaite Capsules/Injection, Aidi Injection, Brucea javanica Oil Injection/Capsules, Xiaoaiping Tablets/Injection, Huachansu Capsules, etc.) within 2 weeks before the first administration;
  4. Patients who have previously received treatment with ROR1 inhibitor drugs;
  5. Patients who have participated in other anti-tumor drug clinical trials within 4 weeks before the first administration (calculated from the last use of the trial drug) and have used the trial drug, or are still within 5 half-lives of the study drug (whichever is shorter).

• Patients with adverse reactions from previous treatments that have not recovered to a Common Terminology Criteria for Adverse Events Version 5.0 (CTC AE v5.0) grade score of ≤1, except for alopecia, non-clinically significant and asymptomatic laboratory abnormalities, and stable hypothyroidism treated with hormone replacement therapy, which are judged by the investigator to have no safety risks.

• Patients who have undergone major surgical treatment, significant traumatic injury, or are expected to undergo major surgery during the study treatment period (except for surgeries specified in the protocol) within 4 weeks before the first administration, or have long-term unhealed wounds or fractures.

• Patients who have experienced any bleeding event ≥ CTC AE v5.0 grade 3 within 4 weeks before the first administration, or have bleeding or coagulation disorders and are using warfarin, aspirin, or other antiplatelet aggregation drugs (except for maintenance doses: aspirin ≤ 100mg/d, clopidogrel ≤ 75mg/d), or have any bleeding signs or history judged by the investigator to be unsuitable for inclusion.

• Patients who have experienced arterial or venous thrombotic events within 6 months before the first administration, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism.

• Patients with decompensated liver cirrhosis (Child-Pugh liver function rating of B or C), active chronic hepatitis B, or active hepatitis C: HbsAg positive and hepatitis B virus (HBV) DNA positive or with a detection value exceeding the lower limit of detection; HCV antibody positive and HCV RNA positive or with a detection value exceeding the lower limit of detection.

Note: For eligible HbsAg positive patients with hepatitis B, regardless of whether HBV DNA is detectable, continuous antiviral treatment (recommended nucleotide analogues) and regular monitoring of HBV DNA are required; for patients with positive HBcAb but negative HbsAg, regular monitoring of HBV DNA is required, and preventive antiviral treatment is recommended; for patients with hepatitis C, regular monitoring of hepatitis C virus (HCV) RNA is required.

• Patients with active syphilis requiring treatment.

• Patients with active pulmonary tuberculosis, a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia, radiation pneumonitis requiring treatment, or active pneumonia with clinical symptoms. (10) Subjects with a history of substance abuse of psychotropic drugs and unable to quit or with mental disorders.

• Subjects with a history of decompensated liver cirrhosis and hepatic encephalopathy.

• Subjects with clinically significant cardiovascular diseases, including any of the following conditions:

  1. Subjects who have experienced acute myocardial infarction or severe/unstable angina within 6 months before the start of study treatment; or subjects with New York Heart Association (NYHA) functional classification of grade 2 or higher heart failure;
  2. Subjects with prolonged QT interval corrected by the Fridericia formula (QTcF) at rest, with QTc ≥ 450 ms (male) or QTc ≥ 470 ms (female);
  3. Subjects with a history of or ongoing severe uncontrolled ventricular arrhythmias requiring drug treatment;
  4. Left ventricular ejection fraction (LVEF) < 50%;
  5. Congenital long QT syndrome or any known history of torsades de pointes (TdP);
  6. Uncontrolled hypertension (after standard antihypertensive treatment, systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 90 mmHg), or a history of hypertensive encephalopathy/hypertensive crisis.

• Subjects with active or uncontrolled severe infections (≥ CTC AE v5.0 grade 2 infection).

• Subjects with renal failure requiring hemodialysis or peritoneal dialysis.

• Subjects with a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases.

• Subjects with (non-infectious) pneumonia/interstitial lung disease requiring steroid treatment or currently having non-infectious pneumonia/interstitial lung disease or having been hospitalized or treated with therapeutic antibiotics for any active infection within 4 weeks before the start of study treatment, including but not limited to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

• Subjects with a history of or current central nervous system diseases, including but not limited to epilepsy, hemorrhagic/ischemic stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, paralysis, aphasia, mental disorders, consciousness disorders, unexplained coma, neuropathy, organic brain syndrome, etc.; and subjects who have experienced cerebrovascular accidents, cerebral infarction, etc. within 6 months before the first dose.

• Subjects with urine protein ≥ ++ in routine urine test and confirmed 24-hour urine protein quantification > 1.0 g.

• Poorly controlled diabetes (fasting blood glucose (FBG) > 10 mmol/L).

• Uncontrolled pleural, peritoneal or pericardial effusion requiring repeated drainage or with obvious symptoms. Subjects with only a small amount of pleural effusion, ascites or pericardial effusion shown on imaging, without symptoms and without drainage or other treatment within 2 weeks before enrollment, can be enrolled.

• Subjects known to be allergic to the excipients of the study drug.

• Subjects, as judged by the investigator, with conditions that seriously endanger the safety of the subject or affect the subject's ability to complete the study.