A Study of BL-B01D1 Monotherapy, BL-B01D1 in Combination With Lenvatinib, BL-B01D1 in Combination With PD-1 Monoclonal Antibody, and BL-B01D1 in Combination With PD-1 Monoclonal Antibody and Bevacizumab in Patients With Advanced Hepatocellular Carcinoma

Official title

A Phase II Clinical Study to Evaluate the Efficacy and Safety of BL-B01D1 Monotherapy, BL-B01D1 in Combination With Lenvatinib, BL-B01D1 in Combination With PD-1 Monoclonal Antibody, and BL-B01D1 in Combination With PD-1 Monoclonal Antibody and Bevacizumab in Patients With Advanced Hepatocellular Carcinoma

Overview

This study is a clinical study to explore the efficacy and safety of BL-B01D1 monotherapy, BL-B01D1 in combination with lenvatinib, BL-B01D1 in combination with PD-1 monoclonal antibody, and BL-B01D1 in combination with PD-1 monoclonal antibody and bevacizumab in patients with advanced hepatocellular carcinoma.

Interventions

• Drug BL-B01D1
  Administration by intravenous infusion for a cycle of 3 weeks.
• Drug Lenvatinib
  8mg (body weight \< 60kg), or 12mg (body weight ≥60kg), QD.
• Drug Finotonlimab
  Administration by intravenous infusion for a cycle of 3 weeks.
• Drug Bevacizumab
  Administration by intravenous infusion for a cycle of 3 weeks.

Primary outcome measures

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

Secondary outcome measures (4)

• Progression-free survival (PFS) [Time frame: Up to approximately 24 months]
• Disease Control Rate (DCR) [Time frame: Up to approximately 24 months]
• Duration of Response (DOR) [Time frame: Up to approximately 24 months]
• Treatment Emergent Adverse Event (TEAE) [Time frame: Up to approximately 24 months]

Eligibility criteria

Inclusion criteria

• Sign the informed consent form voluntarily and follow the protocol requirements;
• Gender is not limited;
• Age ≥18 years old and ≤75 years old;
• Expected survival time ≥3 months;
• Patients with advanced HCC confirmed by histology or cytology;
• Consent to provide archived tumor tissue samples or fresh tissue samples from the primary or metastatic lesions;
• At least one measurable lesion meeting the RECIST v1.1 definition was required;
• ECOG score was 0-1;
• The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
• No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
• Organ function level must meet the requirements;
• Coagulation function: international normalized ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (APTT) ≤1.5×ULN;
• Urinary protein ≤2+ or ≤1000mg/24h;
• No cirrhosis or only Child-Pugh A cirrhosis;
• If hepatitis B virus infection is negative or positive, the status of HBV surface antigen (HBsAg) should be confirmed by HBV serological test;
• For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before the start of treatment, a serum or urine pregnancy test must be negative, and the patient must not be lactating; All enrolled patients should take adequate barrier contraception during the entire treatment cycle and for 6 months after the end of treatment.

Exclusion criteria

• Patients with active central nervous system metastases;
• Who had participated in any other clinical trial within 4 weeks before the trial dose;
• Received anti-tumor therapy such as chemotherapy, radiotherapy and biological therapy within 4 weeks before the first use of study drug;
• Had undergone major surgery (investigator-defined) within 4 weeks before the first dose;
• Systemic corticosteroids or immunosuppressive therapy is required within 2 weeks before study dosing;
• Pulmonary disease defined as ≥ grade 3 according to NCI-CTCAE v5.0; A history of ILD/pulmonary inflammation requiring steroid treatment;
• Serious systemic infection within 4 weeks before screening;
• Patients at risk for active autoimmune disease or with a history of autoimmune disease;
• Other malignant tumors within 5 years before the first treatment;
• Human immunodeficiency virus antibody positive, active tuberculosis or hepatitis C virus infection;
• Poorly controlled hypertension by two antihypertensive drugs with different mechanisms;
• Diabetic patients with poor glycemic control;
• Had a history of severe cardiovascular and cerebrovascular diseases;
• Previous history of autologous or allogeneic stem cell, bone marrow or organ transplantation;
• Subjects with clinically significant bleeding or significant bleeding tendency within the previous 4 weeks were screened;
• Patients with massive or symptomatic effusions or poorly controlled effusions;
• Imaging examination showed that the tumor had invaded or wrapped around the chest, neck, pharynx and other large arteries or invaded the pericardium and heart;
• Unstable thrombotic events requiring therapeutic intervention within 6 months before screening;
• Prior treatment with an ADC drug with a topoisomerase I inhibitor as a toxin;
• Patients with a history of allergy to recombinant humanized antibodies or to any excipients of the trial drug;
• The cumulative dose of anthracyclines > 360 mg/m2 in previous (new) adjuvant therapy;
• Pregnant or lactating women;
• Who have a history of psychotropic drug abuse and cannot quit or have mental disorders;
• Other conditions for trial participation were not considered appropriate 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

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhongshan Hospital Fudan University — Shanghai

Identifiers

NCT: NCT06986785 · BL-B01D1-210

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗