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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Solid Tumor
• Intervention / Treatment: Drug: BL-B01D1

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sa Xiao, PHD; Phone Number: +86-15013238943; Email: xiaosa@baili-pharm.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Guangdong Provincial People's Hospital
      • Contact: Kun Wang
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Jiong Wu, PHD; Phone Number: 86+13601637369; Email: wujiong1122@vip.sina.com
      • Principal Investigator: Jiong Wu, PHD
      • Principal Investigator: Jian Zhang, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements;
2. No gender restrictions;
3. Age: ≥18 years and ≤75 years;
4. Expected survival time ≥3 months;
5. 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;
6. Enrolled subjects should not have received prior systemic therapy for unresectable locally advanced or recurrent/metastatic triple-negative breast cancer;
7. Agree to provide archived tumor tissue specimens or fresh tissue samples from primary or metastatic lesions within the past 3 years;
8. Must have at least one measurable lesion as defined by RECIST v1.1;
9. ECOG performance status score of 0 or 1;
10. Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
11. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%;
12. Organ function levels must meet the requirements without transfusion or use of any cell growth factors and/or platelet-raising drugs within 14 days before the first dose of the study drug;
13. Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × ULN;
14. Urine protein ≤2+ or ≤1000 mg/24h;
15. For premenopausal women with childbearing potential, a pregnancy test (serum or urine) must be performed within 7 days before starting treatment, and the result must be negative; they must not be breastfeeding. All enrolled patients (regardless of gender) must use adequate barrier contraception throughout the treatment period and for 6 months after treatment ends.

Exclusion Criteria:

1. 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);
2. History of severe heart disease;
3. Prolonged QT interval, complete left bundle branch block, third-degree atrioventricular block, or severe arrhythmia;
4. Active autoimmune or inflammatory diseases;
5. Diagnosis of other malignancies within 2 years prior to the first dose;
6. Poorly controlled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg) despite the use of two antihypertensive medications;
7. 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;
8. History of interstitial lung disease (ILD), current ILD, or suspected ILD based on imaging during screening;
9. Concurrent pulmonary disease leading to clinically significant respiratory impairment;
10. Unstable deep vein thrombosis, arterial thrombosis, pulmonary embolism, or other thrombotic events requiring therapeutic intervention within 6 months before screening (excluding catheter-related thrombosis);
11. Patients with central nervous system (CNS) metastases and/or carcinomatous meningitis (leptomeningeal metastases);
12. Patients with significant serous cavity effusion, symptomatic effusion, or poorly controlled effusion;
13. History of hypersensitivity to recombinant humanized antibodies or human-mouse chimeric antibodies, or any excipients of BL-B01D1;
14. Imaging findings indicating tumor invasion or encasement of major thoracic, cervical, or pharyngeal blood vessels, unless the investigator deems it does not affect the patient's eligibility for treatment;
15. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
16. Cumulative anthracycline dose >360 mg/m² in prior (neo)adjuvant anthracycline therapy;
17. Positive for human immunodeficiency virus antibody (HIVAb), active tuberculosis, active hepatitis B virus (HBV) infection, or active hepatitis C virus (HCV) infection;
18. Severe infection (CTCAE > Grade 2) within 4 weeks before the first dose of the study drug; signs of active pulmonary infection within 2 weeks before the first dose;
19. Participation in another clinical trial within 4 weeks before the first dose (calculated from the last dose date);
20. Any other condition deemed unsuitable for participation in this clinical trial by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: BL-B01D1; Administration by intravenous infusion; Other Names: BMS-986507; iza-bren; izalontamab brengitecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ia: Dose limiting toxicity (DLT)	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.	Up to 21 days after the first dose
Phase Ia: Maximum tolerated dose (MTD)	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.	Up to 21 days after the first dose
Phase Ib: phase II clinical studies (RP2D)	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.	Up to 21 days after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-Emergent Adverse Event (TEAE)	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-B01D1 . The type, frequency and severity of TEAE will be evaluated during the treatment of BL-B01D1 .	Up to approximately 24 months
Disease Control Rate (DCR)	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]).	Up to approximately 24 months
Duration of Response (DOR)	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.	Up to approximately 24 months
ADA (anti-drug antibody）	The anti-drug antibody of BL-B01D1	Up to approximately 24 months
Nab (neutralizing antibody)	Neutralizing anti-drug antibodies produced by BL-B01D1	Up to approximately 24 months
Objective Response Rate（ORR）	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	Up to approximately 24 months
Progression-free Survival(PFS)	The PFS is defined as the time from the participant's first dose of BL-B01D1 to the first date of either disease progression or death, whichever occurs first.	Up to approximately 24 months
CL (Clearance)	CL in the serum of BL-B01D1 per unit of time will be investigated	Up to approximately 24 months
AUC0-t	AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration	Up to 21 days after the first dose
Cmax	Maximum serum concentration (Cmax) of BL-B01D1 will be investigated	Up to 21 days after the first dose
Tmax	Time to maximum serum concentration (Tmax) of BL-B01D1 will be investigated	Up to 21 days after the first dose
T1/2	Half-life (T1/2) of BL-B01D1 will be investigated	Up to 21 days after the first dose
Ctrough	Ctough is defined as the lowest serum concentration of BL-B01D1 prior to the next dose will be administered	Up to 21 days after the first dose

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborators: SystImmune Inc.; Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jian Zhang, Fudan University; Principal Investigator: Jiong Wu, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 19, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Estimated): September 26, 2025
• Last Update Submitted That Met QC Criteria: September 25, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: BL-B01D1-104

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No