Clinical trial NCT05785039: A Study of BL-B01D1 in Patients With Multiple Solid Tumors, Including Locally Advanced or Metastatic Urinary System Tumors
Official title: Phase IIa/IIb Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BL-B01D1 for Injection in Patients With Multiple Solid Tumors, Including Locally Advanced or Metastatic Urinary System Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Urinary System Tumor
Solid Tumor
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
First posted: 2023-03-27
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase IIa/IIb clinical study to evaluate the safety, tolerability, pharmacokinetics and efficacy of BL-B01D1 for injection in patients with multiple solid tumors such as locally advanced or metastatic urinary system tumors.

Detailed description: Phase IIa: To explore the safety and initial efficacy of BL-B01D1 in a variety of solid tumors such as locally advanced or metastatic urinary system tumors, and further determine RP2D. The preliminary efficacy, pharmacokinetic characteristics and immunogenicity of BL-B01D1 were evaluated. Phase IIb: To explore the efficacy of BL-B01D1 as a single agent RP2D obtained in a Phase IIa clinical study. To evaluate the safety and tolerability, pharmacokinetic characteristics and immunogenicity of BL-B01D1.

Eligibility criteria: 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;
4. Expected survival time ≥3 months;
5. Locally advanced or metastatic urothelial carcinoma and other solid tumors confirmed by histopathology and/or cytology after failure or intolerance to standard treatment or for which standard treatment is currently unavailable or unavailable;
6. Testosterone levels in prostate cancer \&lt; 1.73 nmol/L (50 ng/dL), disease progression before screening, according to the PCWG3 consensus;
7. Agree to provide archived tumor tissue samples or fresh tissue samples of primary or metastatic lesions within 3 years. If the subjects cannot provide tumor tissue samples, they can be enrolled after the evaluation of the investigators if they meet other inclusion and exclusion criteria;
8. At least one measurable lesion (other than prostate cancer), as defined by RECIST v1.1, was required;
9. ECOG 0 or 1;
10. The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0;
11. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
12. With adequate organ function;
13. For premenopausal women who are likely to have children, a pregnancy test must be performed within 7 days before starting treatment, a serum or urine pregnancy test must be negative, and the patient must not be lactating; All enrolled patients (male or female) were advised to use adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.

Exclusion Criteria:

1. Antineoplastic therapy within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral fluorouracil drugs;
2. History of severe cardiovascular and cerebrovascular diseases;
3. Prolonged QT interval, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
4. Active autoimmune and inflammatory diseases;
5. Other malignant tumors that progressed or required treatment within 5 years before the first dose;
6. Patients with poor blood glucose control before the first dose;
7. Hypertension poorly controlled with two antihypertensive drugs before the first dose or previous history of hypertensive crisis or hypertensive encephalopathy;
8. A history of interstitial lung disease (ILD), current ILD, or suspicion of such disease on imaging during screening;
9. Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
10. Were receiving \&gt before the first dose; Long-term systemic corticosteroid therapy with 10mg/ day prednisone or equivalent anti-inflammatory active drugs or any form of immunosuppressive therapy;
11. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening;
12. Patients with central nervous system (CNS) metastases and/or carcinomatous meningitis (meningeal metastases) and/or spinal cord compression;
13. Patients with massive or symptomatic effusions or poorly controlled effusions;
14. Imaging examination indicated that the tumor had invaded or wrapped the large blood vessels of the chest, neck, and pharynx, except that the investigator thought that it would not affect the patient's enrollment in the drug;
15. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of BL-B01D1's excipients;
16. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
17. Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;
18. Had a serious infection within 4 weeks before the first dose of study drug; Indications of active pulmonary infection within 2 weeks before the first dose of study drug;
19. Patients with superior vena cava syndrome should not be rehydrated;
20. Had a history of severe neurological or psychiatric disorders;
21. Imaging examination showed that the tumor had invaded or wrapped the large thoracic vessels;
22. Serious unhealed wounds, ulcers, or fractures, or clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
23. Subjects scheduled to receive live vaccine or within 28 days before the first dose;
24. Other circumstances that the investigator deemed inappropriate for participation in the trial.

Primary outcomes:
measure: Phase IIa: Recommended Phase II Dose (RP2D)
timeFrame: Up to approximately 24 months
measure: Phase IIb: Objective response rate (ORR)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Phase IIa/IIb: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Phase IIa: Objective response rate (ORR)
timeFrame: Up to approximately 24 months
measure: Phase IIb: Progression-free survival (PFS)
timeFrame: Up to approximately 24 months
measure: Phase IIa/IIb: Disease control rate (DCR)
timeFrame: Up to approximately 24 months
measure: Phase IIa/IIb: Duration of response (DOR)
timeFrame: Up to approximately 24 months
measure: Phase IIa/IIb: Cmax
timeFrame: Up to approximately 24 months
measure: Phase IIa/IIb: Tmax
timeFrame: Up to approximately 24 months
measure: Phase IIa: T1/2
timeFrame: Up to approximately 24 months
measure: Phase IIa: AUC0-t
timeFrame: Up to approximately 24 months
measure: Phase IIa: CL
timeFrame: Up to approximately 24 months
measure: Phase IIa/IIb: Ctrough
timeFrame: Up to approximately 24 months
measure: Phase IIa/IIb: Anti-drug antibody (ADA)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University ShangHai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Dingwei Ye, PHD
role: PRINCIPAL_INVESTIGATOR
References: