Clinical trial NCT05470348: A Study of BL-B01D1 in Patients With Unresectable Locally Advanced or Metastatic Breast Cancer and Other Solid Tumors
Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-B01D1 in Patients With Unresectable Locally Advanced or Metastatic Breast Cancer and Other Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Solid Tumor
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: SystImmune Inc.
name: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
First posted: 2022-07-22
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: In phase Ia, the safety and tolerability of BL-B01D1 in patients with unresectable locally advanced or metastatic breast cancer and other solid tumors. investigated to determine the dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of BL-B01D1.

In phase Ib, 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 The preliminary efficacy, pharmacokinetic characteristics, and immunogenicity of BL-B01D1 in patients with locally advanced or metastatic solid tumors will be evaluated.

EGFR and/or HER3 protein expression or gene amplification in tumor pathological tissues will be detected, and the expression of related ligand will be explored to study its correlation with the validity index of BL-B01D1, and the biomarkers will be optimized to further study the correlation between selected biomarkers and initial efficacy.

Eligibility 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

Primary outcomes:
measure: Phase Ia: Dose limiting toxicity (DLT)
timeFrame: Up to 21 days after the first dose
measure: Phase Ib: phase II clinical studies (RP2D)
timeFrame: Up to 21 days after the first dose
measure: Phase Ia: Maximum tolerated dose (MTD)
timeFrame: Up to 21 days after the first dose
Secondary outcomes:
measure: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Cmax
timeFrame: Up to 21 days after the first dose
measure: Tmax
timeFrame: Up to 21 days after the first dose
measure: T1/2
timeFrame: Up to 21 days after the first dose
measure: AUC0-t
timeFrame: Up to 21 days after the first dose
measure: Ctrough
timeFrame: Up to 21 days after the first dose
measure: ADA (anti-drug antibody）
timeFrame: Up to approximately 24 months
measure: Nab (neutralizing antibody)
timeFrame: Up to approximately 24 months
measure: Objective Response Rate（ORR）
timeFrame: Up to approximately 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 24 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 24 months
measure: Progression-free Survival(PFS)
timeFrame: Up to approximately 24 months
measure: CL (Clearance)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Shanghai
country: China
facility: Fudan University ShangHai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Jiong Wu
role: PRINCIPAL_INVESTIGATOR
affiliation: Fudan University
name: Jian Zhang
role: PRINCIPAL_INVESTIGATOR
References: