Breast Cancer, Solid Tumor
Conditions
Brief summary
This study is an open, multicenter, increasing dose and dose extension nonrandomized phase I clinical study to evaluate the safety, tolerability, pharmacokinetics characteristics and preliminary efficacy of BL-B16D1 in patients with unresectable locally advanced or metastatic breast cancer and other solid tumor.
Interventions
DRUGBL-B16D1
Administration by intravenous infusion for a cycle of 3 weeks.
Sponsors
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Sichuan Baili Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Sign the informed consent form voluntarily and follow the protocol requirements; 2. Gender is not limited; 3. Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib); 4. Expected survival time ≥3 months; 5. Patients with histologically and/or cytologically confirmed unresectable locally advanced or metastatic breast cancer and other solid tumors who failed or could not receive standard treatment; 6. Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 3 years; 7. Must have at least one extracranial measurable lesion that meets the RECIST v1.1 definition; 8. ECOG 0 or 1; 9. The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0; 10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%; 11. The organ function level must meet the requirements if the patient has not received blood transfusion or hematopoietic stimulation factor therapy within 14 days before the first dose; 12. Coagulation function: international normalized ratio ≤1.5, and activated partial thromboplastin time ≤1.5ULN; 13. Urinary protein ≤2+ or ≤1000mg/24h; 14. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, serum pregnancy must be negative, and the patient must not be lactating; All enrolled patients (male or female) should use adequate contraception throughout the treatment cycle and for 6 months after completion of treatment.
Exclusion criteria
1. Chemotherapy, biological therapy and other anti-tumor therapies have been used within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil; 2. History of severe heart disease; 3. Prolonged QT interval, complete left bundle branch block, III degree atrioventricular block; 4. Active autoimmune and inflammatory diseases; 5. Patients with other malignant tumors or a history of other malignant tumors; 6. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded; 7. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg); 8. Patients with poor glycemic control; 9. Patients with grade ≥1 radiation pneumonitis according to the RTOG/EORTC definition; Previous history of ILD or current ILD, or suspicion of such disease during screening; 10. Complicated with pulmonary diseases leading to clinically severe respiratory function impairment; 11. Patients with primary central nervous system (CNS) tumors or CNS metastases that had failed local treatment; 12. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of BL-B16D1's excipients; 13. Received previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT); 14. In previous (new) adjuvant anthracyclines, the cumulative dose of anthracyclines for doxorubicin \> 550 mg/m2, epirubicin \> 900 mg/m2 or the equivalent dose of other similar drugs; 15. Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection; 16. Serious infection occurred within 4 weeks before the first dose; Signs of pulmonary infection or active pulmonary inflammation within 2 weeks before the first dose; 17. Patients with massive or symptomatic effusions, or poorly controlled effusions; 18. Had participated in another clinical trial within 4 weeks before the first dose (calculated from the time of the last dose); 19. Had the following eye diseases: a. active infection or corneal ulcer; b. monocular vision; c. a history of corneal transplantation; d. Contact lens dependence; e. Uncontrolled glaucoma; f. Uncontrolled or progressive retinopathy, wet macular degeneration, etc.; 20. Other circumstances that the investigator deemed inappropriate for participation in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ia: Dose limiting toxicity (DLT) | Up to 21 days after the first dose | DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration. |
| Phase Ia: Maximum tolerated dose (MTD) | Up to 21 days after the first dose | MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle . |
| Phase Ib: Recommended Phase II Dose (RP2D) | Up to approximately 24 months | The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of BL-B16D1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| T1/2 | Up to approximately 24 months | Half-life (T1/2) of BL-B16D1 will be investigated. |
| AUC0-t | Up to approximately 24 months | AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration. |
| CL (Clearance) | Up to approximately 24 months | CL in the serum of BL-B16D1 per unit of time will be investigated. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration of BL-B16D1 prior to the next dose will be administered. |
| Treatment-Emergent Adverse Event (TEAE) | Up to approximately 24 months | TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-B16D1 . The type, frequency and severity of TEAE will be evaluated during the treatment of BL-B16D1. |
| Phase Ib: Objective Response Rate (ORR) | Up to approximately 24 months | ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1. |
| Phase Ib: Disease Control Rate (DCR) | Up to approximately 24 months | The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]). |
| Phase Ib: Duration of Response (DOR) | Up to approximately 24 months | The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first. |
| ADA (anti-drug antibody) | Up to approximately 24 months | Frequency of anti-BL-B16D1 antibody (ADA) will be investigated. |
| Cmax | Up to approximately 24 months | Maximum serum concentration (Cmax) of BL-B16D1 will be investigated. |
| Tmax | Up to approximately 24 months | Time to maximum serum concentration (Tmax) of BL-B16D1 will be investigated. |
Countries
China
Contacts
Primary ContactSa Xiao, PHD
Outcome results
None listed