A Study of Lutetium [177Lu]-BL-ARC001 in Patients With Locally Advanced or Metastatic Lung Cancer, Breast Cancer, Head and Neck Squamous Cell Carcinoma and Other Solid Tumors

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

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.

The study is divided into two stages: the dose-escalation phase (Phase Ia) and the cohort-expansion phase (Phase Ib).

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements;
2. No gender restrictions;
3. Age: ≥18 years and ≤75 years (Phase Ia); ≥18 years (Phase Ib);
4. Expected survival time ≥3 months;
5. Histologically or cytologically confirmed locally advanced or metastatic solid tumors that have failed standard treatment;
6. Agreement to provide archived tumor tissue specimens or fresh tissue samples from primary or metastatic lesions within the past 3 years;
7. Must have at least one measurable lesion as defined by RECIST v1.1;
8. ECOG performance status score of 0 or 1;
9. Toxicity from prior antitumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. Organ function levels must meet the requirements;
12. Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × ULN;
13. Urine protein ≤2+ or ≤1000mg/24h;
14. 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:

1. Use of chemotherapy, biological therapy, or immunotherapy within 4 weeks or 5 half-lives prior to the first dose;
2. History of severe heart disease;
3. Prolonged QT interval, complete left bundle branch block, or third-degree atrioventricular block;
4. Active autoimmune or inflammatory diseases;
5. Diagnosis of other malignancies within 5 years prior to the first dose;
6. Hypertension poorly controlled by two antihypertensive medications;
7. History of interstitial lung disease (ILD) requiring hormonal therapy, current ILD, or ≥ Grade 2 radiation pneumonitis;
8. Symptoms of active central nervous system metastasis;
9. History of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient component of 177Lu-BL-ARC001;
10. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
11. Cumulative dose of anthracyclines >360 mg/m² during prior (neo)adjuvant anthracycline therapy;
12. Positive human immunodeficiency virus (HIV) antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
13. Active infection requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;
14. Participation in another clinical trial within 4 weeks prior to the first dose;
15. Pregnant or lactating women;
16. Other conditions deemed by the investigator as unsuitable for participation in this clinical trial.