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

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborator: SystImmune Inc.

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 (phase Ia); ≥18 years old (phase Ib).

4. Expected survival time ≥ 3 months.

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

6. Participants must agree to provide archived tumor tissue specimens or fresh tissue samples of the primary tumor or metastasis; if the participant is unable to provide tumor tissue samples, the investigator will evaluate whether the participant could be enrolled if other criteria are fit to join the group.

7. Participants must have at least one assessable lesion in phase Ia; participants must have at least one measurable lesion that meets the definition of RECIST v1.1 in phase Ib.

8. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1

9. The toxicity of previous anti-tumor therapy has been restored to level ≤1 as defined by NCI-CTCAE V5.0 (except for asymptomatic laboratory abnormalities such as elevated ALP, hyperuricemia, elevated serum amylase/lipase, and elevated blood glucose; except for toxicity that the investigator determined to have no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, hypothyroidism stabilized by hormone replacement therapy, etc.)

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

11. Has adequate organ function before registration, defined as: a) Bone marrow function:

Absolute neutrophil count (ANC) ≥1.5×109/L, Platelet count ≥100×109/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).

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. 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).

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 2 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 lung disease defined as grade ≥2 according to NCI-CTCAE v5.0, or radiation pneumonitis defined as grade ≥1 according to RTOG/EORTC, or interstitial lung disease (ILD).

8. Symptoms of active central nervous system metastasis. However, participants with stable brain metastasis can be included. Stable is defined as: a. With or without antiepileptic drugs, the seizure-free state lasts for more than 12 weeks; b. There is no need to use glucocorticoids; c. Continuous multiple MRI (scanning interval at least 8 weeks) showed a stable state in imaging.

9. Participants who have a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL-B01D1.

10. Participants have a history of organ transplantation or allogeneic stem cell transplantation (Allo-HSCT).

11. In the adjuvant (or neoadjuvant) treatment of anthracyclines, the cumulative dose of anthracyclines is> 360 mg/m2.

12. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number> the lower limit of detection) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA > the lower limit of detection).

13. Participants with active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.

14. Participated in another clinical trial within 4 weeks prior to participating in the study.

15. Other conditions that the investigator believes that it is not suitable for participating in this clinical trial.