A Study of BL-B16D1 in Patients With Unresectable Locally Advanced or Metastatic Breast Cancer and Other Solid Tumors

A 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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Solid Tumor
• Intervention / Treatment: Drug: BL-B16D1

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 1

Contacts and Locations

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

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Jiong Wu
      • Principal Investigator: Jian Zhang
      • Principal Investigator: Jiong Wu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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-B16D1; Participants receive BL-B16D1 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-B16D1; Administration by intravenous infusion for a cycle of 3 weeks.

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)	MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle .	Up to 21 days after the first dose
Phase Ib: Recommended Phase II Dose (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-B16D1.	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 approximately 24 months
Phase Ib: 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
Phase Ib: 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
Phase Ib: 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
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-B16D1 . The type, frequency and severity of TEAE will be evaluated during the treatment of BL-B16D1.	Up to approximately 24 months
Cmax	Maximum serum concentration (Cmax) of BL-B16D1 will be investigated.	Up to approximately 24 months
Tmax	Time to maximum serum concentration (Tmax) of BL-B16D1 will be investigated.	Up to approximately 24 months
T1/2	Half-life (T1/2) of BL-B16D1 will be investigated.	Up to approximately 24 months
CL (Clearance)	CL in the serum of BL-B16D1 per unit of time will be investigated.	Up to approximately 24 months
Ctrough	Ctrough is defined as the lowest serum concentration of BL-B16D1 prior to the next dose will be administered.	Up to approximately 24 months
ADA (anti-drug antibody)	Frequency of anti-BL-B16D1 antibody (ADA) will be investigated.	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborators: 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 26, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: July 2, 2024
• First Submitted That Met QC Criteria: July 2, 2024
• First Posted (Actual): July 10, 2024

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 17, 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-B16D1-103

Drug and device information, study documents

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