A Study of BL-B16D1 in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Other Solid Tumors

Official title

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of BL-B16D1 in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Other Solid Tumors

Overview

This study is an open, multicenter, increasing dose and dose extension nonrandomized phase I clinical study to evaluate the safety, tolerance, pharmacokinetic characteristics and preliminary effectiveness of BL-B16D1 in recurrent or metastatic head and neck squamous cell carcinomas and other solid tumors.

Interventions

• Drug BL-B16D1
  Administration by intravenous infusion for a cycle of 3 weeks.

Primary outcome measures

• Phase Ia: Dose limiting toxicity (DLT) [Time frame: Up to 21 days after the first dose]
• Phase Ia: Maximum tolerated dose (MTD) [Time frame: Up to 21 days after the first dose]
• Phase Ib: Recommended Phase II Dose (RP2D) [Time frame: Up to approximately 24 months]

Secondary outcome measures (11)

• Treatment-Emergent Adverse Event (TEAE) [Time frame: Up to approximately 24 months]
• Cmax [Time frame: Up to approximately 24 months]
• Tmax [Time frame: Up to approximately 24 months]
• T1/2 [Time frame: Up to approximately 24 months]
• AUC0-t [Time frame: Up to approximately 24 months]
• CL (Clearance) [Time frame: Up to approximately 24 months]
• Ctrough [Time frame: Up to approximately 24 months]
• ADA (anti-drug antibody) [Time frame: Up to approximately 24 months]
• Phase Ib: Objective Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Phase Ib: Disease Control Rate (DCR) [Time frame: Up to approximately 24 months]
• Phase Ib: Duration of Response (DOR) [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 (phase Ia); ≥18 years old (phase Ib);
• Expected survival time ≥3 months;
• Patients with pathologically and/or cytologically confirmed recurrent or metastatic head and neck squamous cell carcinoma and other solid tumors who failed or could not receive standard treatment;
• Agreed to provide primary tumors or metastases 3 years archive of tumor tissue samples or fresh tissue samples;
• Must have at least one accord with RECIST v1.1 define measurable lesions;
• ECOG physical status 0 or 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%;
• The organ function level must meet the requirements if the patient has not received blood transfusion or hematopoietic stimulating factor therapy within 14 days before screening;
• Blood coagulation function: international standardization ratio (INR) 1.5 or less, and the part activated clotting time (APTT) live enzymes ULN 1.5 or less;
• Urinary protein ≤2+ or ≤1000mg/24h;
• 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 the patients (no matter male or female) shall be 6 months after the end of the treatment period and adequate precautions.

Exclusion criteria

• 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 drugs such as fluorouracil;
• History of severe heart disease;
• QT prolongation, complete left bundle branch block, III degree atrioventricular block;
• Active autoimmune and inflammatory diseases;
• Before the first delivery within 5 years diagnosed as other malignant tumor;
• Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg);
• Patients with poor glycemic control;
• Present with grade ≥1 radiation pneumonitis according to the RTOG/EORTC definition; Previous history of ILD or current ILD, or suspicion of such disease during screening;
• Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
• There is activity of the central nervous system symptoms;
• Patients with a history of allergy to recombinant humanized or human-mouse chimeric antibodies or to any of the excipients of BL-B16D1;
• Before transplant or allogeneic hematopoietic stem cell transplantation (Allo - HSCT);
• Previous anthracycline-based adjuvant therapy (new), the cumulative dose anthracycline-based drugs > 360 mg/m2;
• Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;
• Severe infection occurred within 4 weeks before the first dose; Signs of pulmonary infection or active pulmonary inflammation within 2 weeks before the first dose;
• Patients with massive or symptomatic effusions or poorly controlled effusions;
• Had participated in another clinical trial within 4 weeks before the first dose (calculated from the time of the last dose);
• Had the following ocular diseases: a. active infection or corneal ulcer; b. monocular vision; c. a history of corneal transplantation; d. Contact lens dependence; e. Uncontrolled glaucoma; f. Uncontrolled or progressive retinopathy, wet macular degeneration, etc.;
• Other circumstances that the investigator deemed inappropriate for participation in the trial.

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

• Shanghai East Hospital — Shanghai

Identifiers

NCT: NCT06469008 · BL-B16D1-102

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗