Clinical trial NCT06349811: A Study of BL-M05D1 in Patients With Locally Advanced or Metastatic Solid Tumors
Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics Characteristics and Preliminary Efficacy of BL-M05D1 in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Locally Advanced or Metastatic Solid Tumors
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
First posted: 2024-04-05
Enrollment: 30
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: This study is an open-label, multicenter, dose-escalation, and extended-enrollment nonrandomized phase I study to evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy of BL-M05D1 in patients with locally advanced or metastatic solid tumors.


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 solid tumors confirmed by histopathology and/or cytology with failure or intolerance to standard treatment or no standard treatment at present;
6. Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 3 years;
7. At least one measurable lesion meeting the RECIST v1.1 definition was required;
8. ECOG 0 or 1;
9. The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. No blood transfusion, no use of cell growth factors and/or platelet-raising drugs within 14 days before screening, and the organ function level must meet the requirements;
12. Coagulation function: international normalized ratio (INR) ≤1.5, 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 performed within 7 days before starting treatment, serum pregnancy 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. Chemotherapy, biological therapy, immunotherapy and other anti-tumor therapies have been used 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 or palliative radiotherapy within 2 weeks before the first dose; Chinese patent medicine within 2 weeks before the first administration;
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 diagnosed within 5 years before the first dose;
6. Hypertension poorly controlled by two antihypertensive drugs;
7. had a history of ILD or a suspicion of such disease on imaging during screening; The patient was diagnosed with grade ≥1 radiation pneumonitis according to the RTOG/EORTC definition;
8. Pulmonary disease defined as grade ≥2 according to CTCAE v5.0; Pulmonary diseases lead to clinically severe respiratory function impairment;
9. patients with poor glycemic control;
10. patients with active central nervous system metastases;
11. Patients with massive or symptomatic effusions, or poorly controlled effusions;
12. Imaging examination showed that the tumor had invaded or wrapped around the chest, neck, pharynx and other large blood vessels;
13. had a history of pulmonary embolism or a thrombotic event requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded;
14. had a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or any of BL-M05D1 ingredients;
15. prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
16. The cumulative dose of anthracyclines \> 360 mg/m2 in previous (new) adjuvant therapy;
17. human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;
18. active infection requiring systemic therapy;
19. had participated in another clinical trial within 4 weeks before the first dose;
20. pregnant or lactating women;
21. The investigator did not consider it appropriate to apply other criteria for participation in the trial.

Primary outcomes:
measure: Phase Ia: Dose limiting toxicity (DLT)
timeFrame: Up to 21 days after the first dose
measure: Phase Ia: Maximum tolerated dose (MTD)
timeFrame: Up to 21 days after the first dose
measure: Phase Ib: Recommended Phase II Dose (RP2D)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Cmax
timeFrame: Up to approximately 24 months
measure: Tmax
timeFrame: Up to approximately 24 months
measure: T1/2
timeFrame: Up to approximately 24 months
measure: AUC0-t
timeFrame: Up to approximately 24 months
measure: CL (Clearance)
timeFrame: Up to approximately 24 months
measure: Ctrough
timeFrame: Up to approximately 24 months
measure: ADA (anti-drug antibody)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Disease Control Rate (DCR)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Duration of Response (DOR)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Lin Shen, PHD
role: PRINCIPAL_INVESTIGATOR
References: