A Study of BL-B01D1 in Patients With Multiple Solid Tumors, Including Recurrent or Metastatic Gynecological Malignancies

Official title

A Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BL-B01D1 for Injection in Patients With Multiple Solid Tumors, Including Recurrent or Metastatic Gynecological Malignancies

Overview

A phase Ib/II clinical study to evaluate the safety, tolerability, pharmacokinetics and efficacy of BL-B01D1 for injection in patients with multiple solid tumors, including recurrent or metastatic gynecological malignancies.

Detailed description

Phase Ib: To explore the safety and initial efficacy of BL-B01D1 in a variety of solid tumors, including recurrent or metastatic gynecological malignancies, to further identify RP2D. To evaluate the initial efficacy of BL-B01D1. The pharmacokinetic characteristics and immunogenicity of BL-B01D1 were further evaluated. Phase II: To explore the efficacy of BL-B01D1 as a single agent RP2D in patients with multiple solid tumors such as recurrent or metastatic gynecological malignancies using Phase Ib clinical studies. To evaluate the safety and tolerance of BL-B01D1. To evaluate the pharmacokinetic characteristics and immunogenicity of BL-B01D1.

Interventions

• Drug BL-B01D1
  Administration by intravenous infusion

Primary outcome measures

• Phase Ib: Recommended Phase II Dose (RP2D) [Time frame: Up to approximately 24 months]
• Phase II: Objective response rate (ORR) [Time frame: Up to approximately 24 months]

Secondary outcome measures (12)

• Phase Ib/II: Treatment-Emergent Adverse Event (TEAE) [Time frame: Up to approximately 24 months]
• Phase Ib: Objective response rate (ORR) [Time frame: Up to approximately 24 months]
• Phase II: Progression-free survival (PFS) [Time frame: Up to approximately 24 months]
• Phase Ib/II: Disease control rate (DCR) [Time frame: Up to approximately 24 months]
• Phase Ib/II: Duration of response (DOR) [Time frame: Up to approximately 24 months]
• Phase Ib/II: Cmax [Time frame: Up to approximately 24 months]
• Phase Ib/II: Tmax [Time frame: Up to approximately 24 months]
• Phase Ib: T1/2 [Time frame: Up to approximately 24 months]
• Phase Ib: AUC0-t [Time frame: Up to approximately 24 months]
• Phase Ib: CL [Time frame: Up to approximately 24 months]
• Phase Ib/II: Ctrough [Time frame: Up to approximately 24 months]
• Phase Ib/II: Anti-drug antibody (ADA) [Time frame: Up to approximately 24 months]

Eligibility criteria

Inclusion criteria

• Voluntarily sign the informed consent form and comply with the protocol requirements;
• Age: ≥18 years and ≤75 years;
• Expected survival time ≥3 months;
• Histologically and/or cytologically confirmed recurrent or metastatic gynecological malignancies with failed standard treatment, intolerance to standard treatment, or no current standard treatment available;
• Agree to provide archived tumor tissue specimens (10 slides) or fresh tissue samples from primary or metastatic lesions within the past 3 years;
• Must have at least one measurable lesion as defined by RECIST v1.1;
• ECOG performance status score of 0 or 1;
• Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
• No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%;
• Organ function levels must meet the requirements without transfusion, albumin, colony-stimulating factors, any cell growth factors, and/or platelet-raising drugs within 14 days before the first dose of the study drug;
• Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × ULN;
• Urine protein ≤2+ or ≤1000 mg/24h;
• For premenopausal women with childbearing potential, a pregnancy test (serum or urine) must be performed within 7 days before starting treatment, and the result must be negative; they must not be breastfeeding. All enrolled patients must use adequate barrier contraception throughout the treatment period and for 6 months after treatment ends.

Exclusion criteria

• Received chemotherapy, biological therapy, immunotherapy, or other antitumor treatments within 4 weeks or 5 half-lives prior to the first dose (6 weeks for mitomycin and nitrosoureas; oral fluorouracil drugs, etc.);
• History of severe heart disease;
• Prolonged QT interval, complete left bundle branch block, third-degree atrioventricular block, or severe arrhythmia;
• Active autoimmune or inflammatory diseases;
• Other malignancies with progression or requiring treatment within 5 years prior to the first dose;
• Poorly controlled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg) despite the use of two antihypertensive medications;
• Poorly controlled blood glucose levels;
• History of interstitial lung disease (ILD), current ILD, or suspected ILD based on imaging during screening;
• Concurrent pulmonary disease leading to clinically significant respiratory impairment;
• Unstable thrombotic events requiring therapeutic intervention within 6 months before screening;
• Patients with central nervous system (CNS) metastases and/or carcinomatous meningitis (leptomeningeal metastases);
• Patients with significant serous cavity effusion, symptomatic effusion, or poorly controlled effusion;
• History of hypersensitivity to recombinant humanized antibodies or human-mouse chimeric antibodies, or any excipients of BL-B01D1;
• Imaging findings indicating tumor invasion or encasement of major thoracic, cervical, or pharyngeal blood vessels;
• Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
• Cumulative anthracycline dose >360 mg/m² in prior (neo)adjuvant anthracycline therapy;
• Positive for human immunodeficiency virus (HIV) antibodies, active tuberculosis, active hepatitis B virus (HBV) infection, or active hepatitis C virus (HCV) infection;
• Severe infection within 4 weeks before the first dose of the study drug; signs of active pulmonary infection within 2 weeks before the first dose;
• Participation in another clinical trial within 4 weeks before the first dose;
• Any other condition deemed unsuitable for participation in this clinical trial by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University ShangHai Cancer Center — Shanghai

Identifiers

NCT: NCT05803018 · BL-B01D1-202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗