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
Overview
- Phase
- Phase 1
- Intervention
- BL-B01D1
- Conditions
- Breast Cancer
- Sponsor
- Sichuan Baili Pharmaceutical Co., Ltd.
- Enrollment
- 36
- Locations
- 2
- Primary Endpoint
- Phase Ia: Dose limiting toxicity (DLT)
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Voluntarily sign the informed consent form and comply with the protocol requirements;
- •No gender restrictions;
- •Age: ≥18 years and ≤75 years;
- •Expected survival time ≥3 months;
- •Histologically and/or cytologically confirmed unresectable locally advanced or metastatic breast cancer and other solid tumors with failed standard treatment, intolerance to standard treatment, no current standard treatment available, or inability to access standard treatment;
- •Enrolled subjects should not have received prior systemic therapy for unresectable locally advanced or recurrent/metastatic triple-negative breast cancer;
- •Agree to provide archived tumor tissue specimens or fresh tissue samples from primary or metastatic lesions within the past 3 years;
- •Must have at least one measurable lesion as defined by RECIST v1.1;
- •ECOG performance status score of 0 or 1;
- •Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
Exclusion Criteria
- •Received biological therapy, immunotherapy, or other antitumor treatments within 4 weeks or 5 half-lives prior to the first dose (6 weeks for mitomycin and nitrosoureas; oral fluorouracil drugs such as tegafur/gimeracil/oteracil (S-1) or capecitabine, or oral endocrine therapy, or palliative radiotherapy within 2 weeks before the first dose);
- •History of severe heart disease;
- •Prolonged QT interval, complete left bundle branch block, third-degree atrioventricular block, or severe arrhythmia;
- •Active autoimmune or inflammatory diseases;
- •Diagnosis of other malignancies within 2 years prior to the first dose;
- •Poorly controlled hypertension (systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg) despite the use of two antihypertensive medications;
- •Poorly controlled blood glucose (defined as: a) two fasting blood glucose levels \>10 mmol/L, or b) glycated hemoglobin level exceeding 8%), or concurrent diabetic gangrene;
- •History of interstitial lung disease (ILD), current ILD, or suspected ILD based on imaging during screening;
- •Concurrent pulmonary disease leading to clinically significant respiratory impairment;
- •Unstable deep vein thrombosis, arterial thrombosis, pulmonary embolism, or other thrombotic events requiring therapeutic intervention within 6 months before screening (excluding catheter-related thrombosis);
Arms & Interventions
BL-B01D1
Participants receive BL-B01D1 as intravenous infusion for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
Intervention: BL-B01D1
Outcomes
Primary Outcomes
Phase Ia: Dose limiting toxicity (DLT)
Time Frame: 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 Ib: phase II clinical studies (RP2D)
Time Frame: Up to 21 days after the first dose
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-B01D1.
Phase Ia: Maximum tolerated dose (MTD)
Time Frame: Up to 21 days after the first dose
In the dose escalation stage, MTD was selected as the highest dose whose DLT rate estimate was closest to the target DLT rate, but did not exceed the upper bound of the EQUIVALENT interval of DLT rate.
Secondary Outcomes
- Cmax(Up to 21 days after the first dose)
- Nab (neutralizing antibody)(Up to approximately 24 months)
- Ctrough(Up to 21 days after the first dose)
- ADA (anti-drug antibody）(Up to approximately 24 months)
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Tmax(Up to 21 days after the first dose)
- T1/2(Up to 21 days after the first dose)
- AUC0-t(Up to 21 days after the first dose)
- Duration of Response (DOR)(Up to approximately 24 months)
- Objective Response Rate（ORR）(Up to approximately 24 months)
- Disease Control Rate (DCR)(Up to approximately 24 months)
- CL (Clearance)(Up to approximately 24 months)
- Progression-free Survival(PFS)(Up to approximately 24 months)