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

NCT05262491 | Recruiting Phase 1

• 1 other identifier: BL-B01D1-103
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 6

Brief Summary

In phase Ia study, the safety and tolerability of BL-B01D1 in patients with locally advanced or metastatic gastrointestinal tumor and other 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 gastrointestinal tumor and other solid tumor will be evaluated.

Conditions

Gastrointestinal Tumor

Keywords

Esophageal Cancer (EC); Gastric Cancer (GC); Pancreatic Cancer (PC); Colorectal Cancer (CRC)

Outcome Measures

Primary Outcomes (3)

• 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-B01D1

  Up to 21 days after the first dose

Secondary Outcomes (13)

• Treatment-Emergent Adverse Event (TEAE)

  Up to approximately 24 months

• Cmax

  Up to 21 days after the first dose

• 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

Study Arms (1)

Study treatment

EXPERIMENTAL

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

Interventions

BL-B01D1 DRUG

Administration by intravenous infusion

Also known as: iza-bren, izalontamab brengitecan, BMS-986507

Study treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must sign the informed consent form voluntarily and follow the plan requirements.
• No gender limit.
• Age: ≥18 years old and ≤75 years old (phase Ia); ≥18 years old (phase Ib).
• Expected survival time ≥ 3 months.
• Patients with locally advanced or metastatic triple-negative breast cancer or other solid tumors who have been diagnosed histopathologically and/or cytologically as failing standard therapy, or who are not eligible for standard therapy at this stage, and who are inoperable.
• Agree to provide archived tumor tissue samples or fresh tissue samples from the primary tumor or metastatic tumor within 3 years (TROP2 protein expression in tumor pathological tissue to explore the correlation between TROP2 protein expression and BL-M02D1 validity index); If subjects are unable to provide tumor tissue samples, they will be admitted after evaluation by the investigator if other admission criteria are met.
• Participants must have at least one assessable lesion as defined by RECIST V1.1.
• Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1
• The toxicity of previous antitumor therapy was restored to ≤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, grade 2 peripheral neurotoxicity, were excluded).
• Has adequate organ function before registration, defined as: a) Bone marrow function: Absolute neutrophil count (ANC) ≥1.5×109/L, Platelet count ≥90×109/L, Hemoglobin ≥90 g/L; B) Hepatic function: Total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5 ULN for participants without liver metastasis, AST and ALT ≤5.0 ULN for liver metastases; c) Renal function: Creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to the Cockcroft and Gault formula).
• Coagulation function: International normalized ratio (INR)≤1.5, and activated partial thromboplastin time (APTT)≤1.5ULN.
• Urinary protein ≤2+ or ≤1000mg/24h.
• 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. Adequate barrier contraceptive measures should be taken during the treatment and 6 months after the end of treatment for all participants (regardless of male or female).

You may not qualify if:

• Patients screened for any of the following conditions will not be included in this study:
• 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.
• Prior treatment with ADC drugs targeting TROP2 or ADC drugs using camptothecin derivatives (topoisomerase I inhibitors) as toxins.
• 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.
• Participants with prolonged QT interval (male QTc\> 450 msec or female QTc\> 470 msec), complete left bundle branch block, III grade atrioventricular block.
• 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).
• The presence of a second primary tumor within 5 years prior to initial administration, except for radical basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radical resected carcinoma in situ.
• Screening for unstable thrombotic events such as deep vein thrombosis, arterial thrombosis and pulmonary embolism requiring therapeutic intervention within the first 6 months; Infusion device-related thrombosis is excluded;
• 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.
• 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.
• Patients with a history of allergy to recombinant humanized antibody or mouse chimeric antibody or to any excipients of BL-B01D1.
• Previous recipients of organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT).
• In previous adjuvant therapy with anthracyclines, the cumulative dose of anthracyclines was \> 360 mg/m2.
• Positive human immunodeficiency virus antibody (HIVAb), active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number \> 103IU/ml) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA \> lower limit of detection).
• Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, septicemia, etc.

Sponsors & Collaborators

• Sichuan Baili Pharmaceutical Co., Ltd.: lead
• SystImmune Inc.: collaborator
• Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.: collaborator

Study Sites (6)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100037, China

RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

RECRUITING

Jinan Central Hospital

Jinan, Shandong, China

RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, China

RECRUITING

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

RECRUITING

Related Publications (1)

• Liu C, Liu D, Ji Y, Sun M, Gao S, Ma X, Zhong D, Zhu J, Cao Y, Qi C, Zhang M, Zhang P, Xue R, Peng Z, Zhou J, Ge S, Lu M, Yuan J, Wang Y, Wang Z, Li J, Zhang X, Zhu Y, Zhu H, Xiao S, Gong J, Shen L, Lu Z. A bispecific antibody-drug conjugate targeting EGFR and HER3 in metastatic esophageal squamous cell carcinoma: a phase 1b trial. Nat Med. 2025 Oct;31(10):3485-3491. doi: 10.1038/s41591-025-03792-7. Epub 2025 Jul 10.

  PMID: 40640393 DERIVED

MeSH Terms

Conditions

Digestive System Neoplasms; Esophageal Neoplasms; Stomach Neoplasms; Pancreatic Neoplasms; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Neoplasms; Head and Neck Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Lin Shen, PHD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sa Xiao, PHD

CONTACT

+86-15013238943; xiaosa@baili-pharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2022
• First Posted: March 2, 2022
• Study Start: February 14, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 26, 2025

Record last verified: 2025-09

Locations

CN (6)