A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of Lutetium [177Lu]-BL-ARC001 Injection in Patients With Locally Advanced or Metastatic Lung Cancer, Breast Cancer, Head and Neck Squamous Cell Carcinoma and Other Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 22
- Locations
- 1
- Primary Endpoint
- Phase Ia: Dose limiting toxicity (DLT)
Study Overview
Brief Summary
This study is an open, multicenter, dose-escalation and cohort-expansion non-randomized phase I clinical trial to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of Lutetium [177Lu] BL-ARC001 in patients with locally advanced or metastatic solid tumors.
Detailed Description
The study is divided into two stages: the dose-escalation phase (Phase Ia) and the cohort-expansion phase (Phase Ib).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntarily sign the informed consent form and comply with the protocol requirements;
- •No gender restrictions;
- •Age: ≥18 years and ≤75 years (Phase Ia); ≥18 years (Phase Ib);
- •Expected survival time ≥3 months;
- •Histologically or cytologically confirmed locally advanced or metastatic solid tumors that have failed standard treatment;
- •Agreement to provide archived tumor tissue specimens 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 antitumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
- •No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
- •Organ function levels must meet the requirements;
- •Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × ULN;
- •Urine protein ≤2+ or ≤1000mg/24h;
- •For premenopausal women with childbearing potential, a serum pregnancy test must be performed within 7 days before starting treatment, and the result must be negative. Patients must not be breastfeeding; all enrolled patients (regardless of gender) should adopt adequate barrier contraception throughout the treatment cycle and for 6 months after treatment ends.
Exclusion Criteria
- •Use of chemotherapy, biological therapy, or immunotherapy within 4 weeks or 5 half-lives prior to the first dose;
- •History of severe heart disease;
- •Prolonged QT interval, complete left bundle branch block, or third-degree atrioventricular block;
- •Active autoimmune or inflammatory diseases;
- •Diagnosis of other malignancies within 5 years prior to the first dose;
- •Hypertension poorly controlled by two antihypertensive medications;
- •History of interstitial lung disease (ILD) requiring hormonal therapy, current ILD, or ≥ Grade 2 radiation pneumonitis;
- •Symptoms of active central nervous system metastasis;
- •History of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient component of 177Lu-BL-ARC001;
- •Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
- •Cumulative dose of anthracyclines >360 mg/m² during prior (neo)adjuvant anthracycline therapy;
- •Positive human immunodeficiency virus (HIV) antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
- •Active infection requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;
- •Participation in another clinical trial within 4 weeks prior to the first dose;
- •Pregnant or lactating women;
- •Other conditions deemed by the investigator as unsuitable for participation in this clinical trial.
Arms & Interventions
Lutetium [177Lu] BL-ARC001
Participants receive Lutetium [177Lu] BL-ARC001 for the first cycle (6 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
Intervention: Lutetium [177Lu] BL-ARC001 (Drug)
Outcomes
Primary Outcomes
Phase Ia: Dose limiting toxicity (DLT)
Time Frame: Up to 42 days after the first dose
DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.
Phase Ia: Maximum tolerated dose (MTD)
Time Frame: Up to 42 days after the first dose
MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle.
Phase Ib: Recommended Phase II Dose (RP2D)
Time Frame: Up to approximately 24 months
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of Lutetium \[177Lu\] BL-ARC001.
Secondary Outcomes
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Cmax(Up to approximately 24 months)
- Tmax(Up to approximately 24 months)
- T1/2(Up to approximately 24 months)
- AUC0-t(Up to approximately 24 months)
- CL (Clearance)(Up to approximately 24 months)
- Ctrough(Up to approximately 24 months)
- ADA (anti-drug antibody)(Up to approximately 24 months)
- Phase Ib: Objective Response Rate (ORR)(Up to approximately 24 months)
- Phase Ib: Disease Control Rate (DCR)(Up to approximately 24 months)
- Phase Ib: Duration of Response (DOR)(Up to approximately 24 months)