A Study of Lutetium [177Lu] BL-ARC001 in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors

The study is divided into two phases: a dose escalation phase (Phase Ia) and a cohort expansion phase (Phase Ib).

Inclusion criteria

• Voluntarily sign the informed consent form and comply with the protocol requirements;
• Gender: no restriction;
• Age: ≥18 years and ≤75 years (Phase Ia); ≥18 years (Phase Ib);
• Expected survival time ≥3 months;
• Locally advanced or metastatic solid tumors;
• Agree 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 meeting the RECIST v1.1 criteria;
• ECOG performance status score of 0 or 1;
• Toxicities from prior antitumor therapy have 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 ≤1.5, and activated partial thromboplastin time ≤1.5 × ULN;
• Urine 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 must not be breastfeeding; all enrolled patients (regardless of gender) should use adequate barrier contraception throughout the treatment cycle and for 6 months after treatment ends.

Exclusion criteria

• Use of chemotherapy, biotherapy, or immunotherapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose;
• History of severe heart disease;
• QT interval prolongation, 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 steroid treatment, current ILD, or ≥ Grade 2 radiation pneumonitis;
• Symptoms of active central nervous system metastases;
• History of allergy to recombinant humanized or chimeric antibodies, or allergy to any excipient of Lutetium [177Lu] BL-ARC001;
• Previous organ transplantation or allogeneic hematopoietic stem cell transplantation;
• Cumulative dose of anthracyclines > 360 mg/m² in previous (neo)adjuvant anthracycline therapy;
• Positive human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
• Active infection requiring systemic treatment;
• Participation in another clinical trial within 4 weeks prior to the first dose;
• Pregnant or lactating women;
• Any other condition deemed by the investigator as unsuitable for participation in this clinical trial.