A Study of BL-B01D1 in Patients With Locally Advanced or Metastatic Urological Tumors and Other Solid Tumors

• Status: Recruiting
• Trial end date: 2024-04-09
• Target enrollment: 0
• Participant gender: All

Summary

In phase Ia study, the safety and tolerability of BL-B01D1 in patients with locally advanced or metastatic urinary tumors and other solid tumors will be investigated to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) of BL-B01D1.

In phase Ib study, the safety and tolerability of BL-B01D1 at the phase Ia recommended dose will be further investigated, and recommended phase II dose (RP2D) for phase II clinical studies will be determined.

In addition, the preliminary efficacy, pharmacokinetic characteristics, and immunogenicity of BL-B01D1 in patients with locally advanced or metastatic urinary tumors and other solid tumors will be evaluated.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborator: SystImmune Inc.

Criteria

Inclusion Criteria:

1. Participants must sign the informed consent form voluntarily and follow the plan requirements;

2. No gender limit;

3. Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib);

4. Expected survival time ≥ 3 months;

5. Locally advanced or metastatic tumors of the urinary system and other solid tumors confirmed by histopathology and/or cytology, which are incurable or currently without standard treatment. Intolerance refers to the occurrence of grade 3-4 adverse reactions after a patient has received standard treatment, and the patient refuses to continue the original treatment;

6. Agree to provide archived tumor tissue specimens (10 unstained sections (anti-extraction) surgical specimens (thickness 4-5μm)) or fresh tissue samples from primary or metastatic lesions within 3 years. If patients cannot provide such specimens, they can be included in the group after the judgment of the investigator if other inclusion criteria are met;

7. Participants must have at least one measurable lesion that meets the definition of RECIST v1.1;

8. Physical fitness score ECOG 0 or 1 point;

9. The toxicity of previous anti-tumor treatments has been restored to NCI-CTCAE v5.0 definition ≤ 1 (except for hair loss);

10. No serious cardiac dysfunction, left ventricular ejection fraction (LVEF) ≥50%;

11. The organ function must meet the following requirements and standards: a) Bone marrow function: absolute neutrophil count (ANC) ≥1.5×109/L, platelet count ≥75×109/L, hemoglobin ≥90 g/L; B) Liver function: total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5 ULN for participants without liver metastasis, AST and ALT ≤5.0 ULN for liver metastases; c) Kidney function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to the Cockcroft and Gault formula);

12. Coagulation function: International normalized ratio (INR)≤1.5×ULN, and activated partial thromboplastin time (APTT)≤1.5ULN;

13. For premenopausal women with childbearing potential, a pregnancy test must be taken within 7 days prior to the start of treatment. Serum or urine pregnancy must be negative and must be non-lactating; all participants (regardless of male or female) in the group should be treated throughout the treatment. Adequate barrier contraceptive measures should be taken during the treatment and 6 months after the treatment.

Exclusion Criteria:

1. Prior use of antibody-coupled drugs (ADC);

2. Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other anti-tumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration; oral fluorouracil-like drugs such as S-1, capecitabine, or palliative radiotherapy within 2weeks prior to the first administration;

3. Have a history of serious cardiovascular and cerebrovascular diseases, including but not limited to:

1. Have serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias and ⅲ degree ATrioventricular block requiring clinical intervention;

2. QT interval was prolonged in resting state (QTc > 450 msec for men or 470 msec for women);

3. Myocardial infarction, unstable angina, cardiac angioplasty or stent implantation, coronary artery/peripheral artery bypass graft, Class ⅲ or ⅳ congestive heart failure, cerebrovascular accident, or transient ischemic attack within 6 months prior to the first administration;

4. Active autoimmune diseases and inflammatory diseases, such as: systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, etc., except for type I diabetes, hypothyroidism that can be controlled only by alternative treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis);

5. Other malignant tumors were diagnosed within 2 years prior to the first administration with the following exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after radical resection;

6. Participants have grade 3 lung disease defined according to NCI-CTCAE v5.0, or a history of interstitial lung disease (ILD);

7. Symptoms of active central nervous system metastasis. However, participants with stable brain metastasis can be included. Stable is defined as:

1. The seizureless state lasted for > 3 months with or without antiepileptic drugs;

2. Central nervous system (CNS) metastases and/or cancerous meningitis. Subjects who have been treated with BMS who have been stable for at least 3 months, who have no disease progression determined by imaging within 28 days prior to initial treatment with the study drug, and who have returned all neurological symptoms to grade ≤1 (CTCAE5.0) or baseline (other than signs or symptoms associated with CNS treatment) for at least 2 weeks, Patients with no evidence of new or expanded BMS and a prednisone treatment dose of 20mg/ day or less (or equivalent) within 7 days prior to initial treatment with the study drug were eligible for inclusion in the study. Cancerous meningitis, whether clinically stable or not, should be excluded;

8. Participants who have a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL-B01D1;

9. Participants have a history of autologous or allogeneic stem cell transplantation（Allo-HSCT);

10. In the adjuvant (or neoadjuvant) treatment of anthracyclines, the cumulative dose of anthracyclines is> 360 mg/m2;

11. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number> the lower limit of detection) or active hepatitis C virus infection(HCV antibody positive and HCV-RNA > the lower limit of detection);

12. Participants with active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc;

13. Other conditions that the investigator believes that it is not suitable for participating in this clinical trial.