A Study of BL-B01D1 in Patients With Locally Advanced or Metastatic Solid Tumor

NCT ID: NCT05194982

Last Updated: 2025-09-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 570 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-29
• Study Completion Date: 2027-12-31

Brief Summary

In phase Ia study, the safety and tolerability of BL-B01D1 in patients with locally advanced or metastatic solid tumor will be investigated to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) of BL-B01D1.

In phase Ib study, 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.

In addition, the preliminary efficacy, pharmacokinetic characteristics, and immunogenicity of BL-B01D1 in patients with locally advanced or metastatic solid tumor will be evaluated.

Conditions

Locally Advanced or Metastatic Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Study treatment

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.

Group Type: EXPERIMENTAL

BL-B01D1

Intervention Type: DRUG

Administration by intravenous infusion.

Interventions

BL-B01D1

Administration by intravenous infusion.

Intervention Type: DRUG

Other Intervention Names

iza-bren; izalontamab brengitecan; BMS-986507

Eligibility Criteria

Inclusion Criteria

1. Participants must sign the informed consent form voluntarily and follow the plan requirements.

2. No gender limit.

3. Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib).

4. Expected survival time ≥ 3 months.

5. Locally advanced or metastatic solid tumor confirmed by histopathology and/or cytology, which are incurable or currently without standard treatment.

7. Participants must have at least one measurable lesion that meets the definition of RECIST v1.1.

8. Physical fitness score ECOG 0 or 1 point

9. Toxicity of previous antitumor therapy has returned to ≤ level 1 as defined by NCI-CTCAE v5.0 (except for asymptomatic laboratory abnormalities considered by the investigators, such as elevated ALP, hyperuricemia, and elevated blood glucose; Toxicities with no safety risk, such as hair loss and grade 2 peripheral neurotoxicity, were excluded. Or decreased hemoglobin except ≥90 g/L).

10. No serious cardiac dysfunction, left ventricular ejection fraction (LVEF) ≥50%

11. The organ function level must meet the following requirements: a) bone marrow function: absolute neutrophilic granulocyte count (ANC) ≥1.5×109/L, platelet count ≥90×109/L, hemoglobin ≥90 g/L; b) Liver function: total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5 ULN in patients without liver metastasis, AST and ALT ≤5.0 ULN in patients with liver metastasis; c) Kidney function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to Cockcroft and Gault formula).

12. Coagulation function: International normalized ratio (INR)≤1.5×ULN, and activated partial thromboplastin time (APTT)≤1.5ULN.

13. Urinary protein ≤2+ or ≤1000mg/24h.

14. For premenopausal women with childbearing potential, a pregnancy test must be taken within 7 days prior to the start of treatment. Serum or urine pregnancy must be negative and must be non-lactating; all participants (regardless of male or female) in the group should be treated throughout the treatment. Adequate barrier contraceptive measures should be taken during the treatment and 6 months after the treatment.

Exclusion Criteria

1. Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other anti-tumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration; oral fluorouracil-like drugs such as S-1, capecitabine, or palliative radiotherapy within 2weeks prior to the first administration.

2. Participants with history of severe heart disease, such as: symptomatic congestive heart failure (CHF) ≥ grade 2 (CTCAE 5.0), New York Heart Association (NYHA) ≥ grade 2 heart failure, history of transmural myocardial infarction, unstable angina pectoris etc.

3. Participants with prolonged QT interval (male QTc> 450 msec or female QTc> 470 msec), complete left bundle branch block, III grade atrioventricular block.

4. Active autoimmune diseases and inflammatory diseases, such as: systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, etc., except for type I diabetes, hypothyroidism that can be controlled only by alternative treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis).

5. Other malignant tumors were diagnosed within 5 years prior to the first administration with the following exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after radical resection.

6. Participants with poorly controlled hypertension by two kinds of antihypertensive drugs (systolic blood pressure>150 mmHg or diastolic blood pressure>100 mmHg).

7. Participants have grade 3 lung disease defined according to NCI-CTCAE v5.0, or a history of interstitial lung disease (ILD).

8. Unstable thrombotic events such as deep vein thrombosis, arterial thrombosis and pulmonary embolism requiring therapeutic intervention within 6 months prior to screening; Thrombus formation associated with infusion set is excluded.

9. Symptoms of active central nervous system metastasis. However, patients with stable brain parenchymal metastases can be enrolled. Stable was defined as: a. The seizure-free state lasted for > 12 weeks with or without the use of antiepileptic drugs; b. Glucocorticoid use is not required; c. Consecutive MRI scans (at least 8 weeks between scans) showed stable imaging status.

10. Patients with a history of allergy to recombinant humanized antibody or mouse chimeric antibody or to any excipients of BL-B01D1.

11. Previous recipients of organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT).

12. In previous adjuvant therapy with anthracyclines, the cumulative dose of anthracyclines was > 360 mg/m2.

13. Positive human immunodeficiency virus antibody (HIVAb), active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > 103 IU/ml) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA > lower limit of detection).

14. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, septicemia, etc.

15. Participated in another clinical trial (calculated from the time of the last dose) within 4 weeks prior to the first dose.

16. The other conditions of participation in this clinical trial were not considered appropriate by the investigators.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SystImmune Inc.

INDUSTRY

Sponsor Role: collaborator

Sichuan Baili Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Li Zhang, PHD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

Site Status: RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

The Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Renmin Hospital of Wuhan University

Wuhan, Hubei, China

Site Status: RECRUITING

Union Hospital Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status: RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status: RECRUITING

Shanghai Oriental Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Shanxi Cancer Hospital

Taiyuan, Shanxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Sa Xiao, PHD

Role: CONTACT

xiaosa@baili-pharm.com

+86-15013238943

Facility Contacts

Yongsheng Li

Role: primary

Li Zhang, PHD

Role: primary

zhangli6@mail.sysu.edu.cn

020-87343458

Jun Yang

Role: primary

Zhenming Fu

Role: primary

Kunyu Yang

Role: primary

Yaqian Han

Role: primary

Ye Guo

Role: primary

Weihua Yang

Role: primary

References

Ma Y, Huang Y, Zhao Y, Zhao S, Xue J, Yang Y, Fang W, Guo Y, Han Y, Yang K, Li Y, Yang J, Fu Z, Chen G, Chen L, Zhou N, Zhou T, Zhang Y, Zhou H, Liu Q, Zhu Y, Zhu H, Xiao S, Zhang L, Zhao H. BL-B01D1, a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, in patients with locally advanced or metastatic solid tumours: a first-in-human, open-label, multicentre, phase 1 study. Lancet Oncol. 2024 Jul;25(7):901-911. doi: 10.1016/S1470-2045(24)00159-1. Epub 2024 May 29.

Reference Type: DERIVED

PMID: 38823410 (View on PubMed)

Other Identifiers

BL-B01D1-101

Identifier Type: -

Identifier Source: org_study_id