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

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

In this study, the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), recommended phase II dose (RP2D), the preliminary efficacy, pharmacokinetic characteristics, and immunogenicity of BL-B01D1 will be investigated in patients with unresectable locally advanced or metastatic breast cancer and other solid tumors.

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

Details

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

Criteria

Inclusion Criteria:

• 1. Sign the informed consent voluntarily and follow the program requirements;

• 2. No gender limitation;

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

• 4. Expected survival time ≥3 months;

• 5. Failure or intolerance to standard treatment confirmed by histopathology and/or cytology or no standard treatment currently available or unresectable locally advanced or metastatic breast cancer and other solid tumors for which standard treatment is not available;

• 6. Agree to provide archived tumor tissue samples or fresh tissue samples of primary or metastatic tumor within 3 years; If subjects are unable to provide tumor tissue samples, they will be admitted after evaluation by the investigator if other admission criteria are met.

• 7. Must have at least one measurable lesion as defined by RECIST V1.1;

• 8. ECOG score of 0 or 1;

• 9. Toxicity from previous antitumor therapy has returned to level ≤1 as defined by NCI-CTCAE V5.0

• 10. No serious cardiac dysfunction, left ventricular ejection fraction ≥50%;

• 11. Organ function level must meet the following requirements and meet the following standards: A) Bone marrow function: absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet count ≥100×10^9/L, hemoglobin ≥90 g/L; B) Liver function: total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5ULN in patients without liver metastasis, AST and ALT ≤5.0 ULN in patients with liver metastasis; C) Renal function: Creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min.

• 12. Coagulation function: International standardized ratio (INR) ≤1.5, and activated partial thrombin time (APTT) ≤1.5ULN;

• 13. Urinary protein ≤2+ or ≤1000mg/24h;

• 14. For premenopausal women who are likely to have children, a pregnancy test must be performed within 7 days of the start of treatment. Serum or urine pregnancy must be negative and must be non-lactation; All enrolled patients (male and female) should use adequate barrier contraception throughout the treatment cycle and 6 months after the end of treatment.

Exclusion Criteria:

• 1. Prior treatment with ADC drugs using camptothecin derivatives (topoisomerase I inhibitors) as toxins;

• 2. Use of chemotherapy, biotherapy, immunotherapy, radical radiotherapy, major surgery (as defined by the investigator), targeted therapy (including small molecule tyrosine kinase inhibitors) and other antitumor therapies within 4 weeks or 5 half-lives, whichever is less, prior to initial dosing; Mitomycin and nitrosourea were administered within 6 weeks prior to initial administration; Fluorouracil oral agents such as ticio, capecitabine, oral endocrine therapy, or palliative radiotherapy within 2 weeks before initial administration;

• 3. History of severe heart disease, such as symptomatic congestive heart failure (CHF) ≥2 (CTCAE 5.0), Heart failure (NYHA) ≥2, history of transmural myocardial infarction, unstable angina, etc

• 4. QT prolongation (male QTc > 450 msec or female QTc > 470 msec), complete left bundle branch block, III atrioventricular block;

• 5. Active autoimmune and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, are excluded from type I sugars urinary diseases, hypothyroidism that can be controlled only by alternative therapy, skin diseases that do not require systemic treatment (e.g., vitiligo, psoriasis);

• 6. Other malignant tumors were diagnosed within 2 years prior to first administration, except for radical basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radical resected carcinoma in situ;

• 7. Hypertension poorly controlled by two antihypertensive medications (systolic blood pressure & GT; 150 mmHg or diastolic pressure & GT; 100 mmHg);

• 8. Lung disease defined as grade ≥2 according to CTCAE V5.0, and now defined according to RTOG/EORTC Grade ≥1 radiation pneumonia; Existing patients with interstitial lung disease (ILD);

• 9. Screening for unstable thrombotic events such as deep vein thrombosis, arterial thrombosis and pulmonary embolism requiring therapeutic intervention within the first 6 months; Infusion device-related thrombosis is excluded;

• 10. Primary central nervous system (CNS) malignancy; Patients with CNS metastasis who have failed local treatment (excluding asymptomatic BMS, or those with stable clinical symptoms and no steroid or other treatment for BMS for ≥28 days);

• 11. Patients with uncontrolled pleural and abdominal effusion with clinical symptoms, judged by the investigator to be unsuitable for inclusion;

• 12. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any excipient component of BL-B01D1;

• 13. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (ALLO-HSCT);

• 14. Cumulative dose of anthracyclines > 360 mg/m^2 in previous anthracyclines (new) adjuvant therapy

• 15. Positive human immunodeficiency virus antibody (HIVAb), active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > 10^3IU/ml) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA > lower limit of detection);

• 16. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.

• 17. Participated in another clinical trial within 4 weeks prior to initial administration (starting from the time of last administration);

• 18. Other conditions considered inappropriate for participation in this clinical trial by the investigator