Gastrointestinal Tumors, Solid Tumors
Conditions
Brief summary
This study is an open-label, multicenter, non-randomized Phase I clinical trial to evaluate the safety, tolerability, pharmacokinetic profile, 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 phases: a dose escalation phase (Phase Ia) and a cohort expansion phase (Phase Ib).
Interventions
Administration by intravenous infusion for a cycle of 6 weeks.
Sponsors
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Sichuan Baili Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntarily sign the informed consent form and comply with the protocol requirements; 2. Gender: no restriction; 3. Age: ≥18 years and ≤75 years (Phase Ia); ≥18 years (Phase Ib); 4. Expected survival time ≥3 months; 5. Locally advanced or metastatic solid tumors; 6. Agree 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 meeting the RECIST v1.1 criteria; 8. ECOG performance status score of 0 or 1; 9. Toxicities from prior antitumor therapy have 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 ≤1.5, and activated partial thromboplastin time ≤1.5 × ULN; 13. Urine protein ≤2+ or ≤1000mg/24h; 14. 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
1. Use of chemotherapy, biotherapy, or immunotherapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose; 2. History of severe heart disease; 3. QT interval prolongation, 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 steroid treatment, current ILD, or ≥ Grade 2 radiation pneumonitis; 8. Symptoms of active central nervous system metastases; 9. History of allergy to recombinant humanized or chimeric antibodies, or allergy to any excipient of Lutetium \[177Lu\] BL-ARC001; 10. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation; 11. Cumulative dose of anthracyclines \> 360 mg/m² in previous (neo)adjuvant anthracycline therapy; 12. Positive human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection; 13. Active infection requiring systemic treatment; 14. Participation in another clinical trial within 4 weeks prior to the first dose; 15. Pregnant or lactating women; 16. Any other condition deemed by the investigator as unsuitable for participation in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ia: Dose limiting toxicity (DLT) | 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) | 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| T1/2 | Up to approximately 24 months | Half-life (T1/2) of Lutetium \[177Lu\] BL-ARC001 will be investigated. |
| AUC0-t | Up to approximately 24 months | AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration. |
| CL (Clearance) | Up to approximately 24 months | CL in the serum of Lutetium \[177Lu\] BL-ARC001 per unit of time will be investigated. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration of Lutetium \[177Lu\] BL-ARC001 prior to the next dose will be administered. |
| ADA (anti-drug antibody) | Up to approximately 24 months | Frequency of anti-Lutetium \[177Lu\] BL-ARC001 antibody (ADA) will be investigated. |
| Treatment-Emergent Adverse Event (TEAE) | Up to approximately 24 months | TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of Lutetium \[177Lu\] BL-ARC001. The type, frequency and severity of TEAE will be evaluated during the treatment of Lutetium \[177Lu\] BL-ARC001. |
| Radiation Characteristics | Up to approximately 24 months | The radiation characteristics of Lutetium \[177Lu\] BL-ARC001 will be investigated. |
| Phase Ib: Objective Response Rate (ORR) | Up to approximately 24 months | ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1. |
| Phase Ib: Disease Control Rate (DCR) | Up to approximately 24 months | The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]). |
| Phase Ib: Duration of Response (DOR) | Up to approximately 24 months | The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first. |
| Distribution Characteristics | Up to approximately 24 months | The distribution characteristics of Lutetium \[177Lu\] BL-ARC001 will be investigated. |
| Cmax | Up to approximately 24 months | Maximum serum concentration (Cmax) of Lutetium \[177Lu\] BL-ARC001 will be investigated. |
| Tmax | Up to approximately 24 months | Time to maximum serum concentration (Tmax) of Lutetium \[177Lu\] BL-ARC001 will be investigated. |
Countries
China
Contacts
Primary ContactSa Xiao, PHD
Outcome results
None listed