Trial Title:
Phase I Clinical Study of BL-M07D1 in Locally Advanced or Metastatic Digestive Tract Tumors and Other Solid Tumors
NCT ID:
NCT05631964
Condition:
Locally Advanced or Metastatic Digestive Tract Tumors
Other Solid Tumors
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BL-M07D1
Description:
Administration by intravenous infusion
Arm group label:
Study treatment
Summary:
Evaluation of BL-M07D1 for injection in Phase I clinical study of safety, tolerability,
pharmacokinetic Characteristics, and initial efficacy in patients with locally advanced
or metastatic digestive tract tumors and other solid tumors.
Detailed description:
Phase Ia: To observe the safety and tolerability of BL-M07D1 in patients with locally
advanced or metastatic digestive tract tumors and other solid tumors, determine the MTD
and DLT of BL-M07D1, and evaluate the pharmacokinetic characteristics and immunogenicity
of BL-M07D1. Phase Ib: To further observe the safety and tolerability of BL-M07D1 at the
Phase Ia recommended dose and determine RP2D. To evaluate the initial efficacy,
pharmacokinetic characteristics and immunogenicity of BL-M07D1.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Sign informed consent voluntarily and follow protocol requirements.
2. No gender limitation.
3. Age: ≥18 years and ≤75 years (phase Ia); ≥18 years old (phase Ib).
4. The expected survival time is ≥3 months.
5. Patients with locally advanced or metastatic HER2-positive/low-expression digestive
tract tumors and other solid tumors that are not operable and have been confirmed by
histopathology and/or cytology, have failed standard therapy, are not available for
standard therapy, or are not currently applicable for standard therapy; HER2
positive: IHC 3+, or IHC 2+ and ISH positive; Low HER2 expression: IHC 2+ and ISH
negative, or IHC 1+.
6. Agree to provide archived tumor tissue samples or fresh tissue samples from the
primary or metastatic lesion within 2 years (to detect HER2 expression or
amplification in tumor pathological tissue and explore its correlation with
effectiveness indicators of BL-M07D1); If a subject is unable to provide a tumor
tissue sample, he/she may be enrolled after an investigator's evaluation if other
admission criteria are met.
7. There must be at least one measurable lesion that meets the RECIST v1.1 definition.
8. ECOG score 0 or 1.
9. 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, hyperpigmentation, grade 2
peripheral neurotoxicity, etc.).
10. No serious cardiac abnormality, left ventricular ejection fraction ≥50%.
11. The level of organ function must meet the following requirements and meet the
following standards:
1. Bone marrow function: absolute neutrophil count (ANC) ≥1.5×109/L, platelet
count ≥100×109/L, hemoglobin ≥90 g/L;
2. 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;
3. Kidney function: Creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50
mL/min (based on Cockcroft and Gault formula).
12. Coagulation function: International Standardized ratio (INR) ≤1.5, and activated
partial thrombin time (APTT) ≤1.5ULN.
13. Urine protein ≤2+ or ≤1000mg/24h.
14. Albumin ≥30 g/L.
15. A pregnancy test must be performed within 7 days of starting treatment for
premenopausal women who are likely to have children, the serum/urine pregnancy must
be negative, and the pregnancy must be non-lactation; All enrolled patients (male or
female) should take adequate barrier contraception throughout the treatment cycle
and for 6 months after the end of treatment.
Exclusion Criteria:
1. Antitumor therapy such as chemotherapy, biotherapy, immunotherapy, radical
radiotherapy, major surgery, targeted therapy (including small-molecule tyrosine
kinase inhibitors) within 4 weeks prior to initial administration or within 5
half-lives, whichever is shorter; Mitomycin and nitrosourea were administered within
6 weeks before the first administration. Oral fluorouracil drugs such as Tizio,
capecitabine, or palliative radiotherapy within 2 weeks prior to initial
administration; Traditional Chinese medicines or proprietary Chinese medicines with
anti-tumor indications should be administered within 2 weeks before the first
administration.
2. Previously received ADC drug therapy with camptothecin derivatives (topoisomerase I
inhibitors) as toxins (Phase Ib only).
3. History of severe heart disease, such as symptomatic congestive heart failure (CHF)
≥2 (CTCAE 5.0), New York Heart Society (NYHA) ≥2 heart failure, history of
transmural myocardial infarction, unstable angina, etc.
4. Prolonged QT interval (QTcF > 450 msec in men or 470 msec in women), complete left
bundle branch block, and degree III atrioventricular block.
5. Active autoimmune or inflammatory diseases, such as systemic lupus erythematosus,
psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel
disease, and Hashimoto's thyroiditis, other than type I diabetes, hypothyroidism
that can be controlled by alternative therapy alone, skin diseases that do not
require systemic treatment (e.g., vitiligo, psoriasis).
6. Other malignancies developed within 3 years of enrollment, excluding:(1)radical
cervical carcinoma in situ or non-melanoma skin cancer;(2)the second primary cancer
that has been completely cured and no recurrence within 3 years;(3)The researchers
believed that both primary cancers could benefit from this study;(4)The
investigators have clearly ruled out which primary tumor source the metastases
belong to.
7. 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.
8. The poorly controlled pericardial effusion, pleural effusion and abdominal effusion
with clinical symptoms were not suitable for inclusion by the researchers.
9. Hypertension poorly controlled by antihypertensive medications (systolic blood
pressure > 150 mmHg or diastolic blood pressure > 100 mmHg).
10. According to CTCAE v5.0, patients were defined as ≥3 lung disease, ≥2 radiation lung
disease, present or history of interstitial lung disease (ILD).
11. Patients who received lung radiation therapy within 6 months with total dose ≥30 Gy.
12. Patients with active central nervous system metastases. But the researchers believe
that patients with stable brain parenchymal metastases can be included. The
definition of stability should meet the following four requirements:
1. Seizures-free status lasting > 12 weeks with or without antiepileptic
medication;
2. No need for glucocorticoids;
3. Two consecutive MRI scans (scan interval at least 4 weeks) showed stable
imaging status;
4. Asymptomatic patients stable for more than 1 month after treatment.
13. Patients with a history of allergy to recombinant humanized antibodies or human and
mouse chimeric antibodies or to any excipient component of BL-M07D1.
14. Previous recipients of organ transplantation or allogeneic hematopoietic stem cell
transplantation (Allo-HSCT).
15. In previous treatment with anthracyclines, the equivalent cumulative dose of
doxorubicin was greater than 360 mg/m2.
16. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active
hepatitis B virus infection (HBV-DNA copy number > lower limit of detection) or
active hepatitis C virus infection (HCV antibody positive and HCV-RNA > lower limit
of detection).
17. Active infections requiring systemic treatment, such as severe pneumonia,
bacteremia, sepsis, etc.
18. Had participated in another clinical trial within 4 weeks prior to the first dose
(counting from the time of the last dose).
19. A pregnant or nursing woman.
20. Other conditions included in this clinical trial were not considered appropriate.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University ShangHai Cancer Center
Address:
City:
Shanghai
Zip:
200100
Country:
China
Status:
Recruiting
Contact:
Last name:
WeiJian Guo, PHD
Phone:
021-64175590-73546
Email:
guoweijian1@hotmail.com
Contact backup:
Last name:
Jian Zhang, PHD
Phone:
021-64175590-73546
Email:
Syner2000@163.com
Investigator:
Last name:
WeiJian Guo
Email:
Principal Investigator
Investigator:
Last name:
Jian Zhang
Email:
Principal Investigator
Start date:
January 5, 2023
Completion date:
January 2025
Lead sponsor:
Agency:
Sichuan Baili Pharmaceutical Co., Ltd.
Agency class:
Industry
Collaborator:
Agency:
SystImmune Inc.
Agency class:
Industry
Collaborator:
Agency:
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Sichuan Baili Pharmaceutical Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05631964
