Gastrointestinal Tumors, Solid Tumors
Conditions
Brief summary
This is an open-label, multicenter, non-randomized Phase I clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of BL-ARC002 Injection in patients with locally advanced or metastatic solid tumors.
Detailed description
The study consists of two phases: a dose-escalation phase (Phase Ia) and an expansion cohort phase (Phase Ib).
Interventions
DRUGBL-ARC002
Administration by intravenous infusion for a cycle of 6 weeks.
Sponsors
Sichuan Baili Pharmaceutical Co., Ltd.
Baili-Bio (Chengdu) 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 agree to comply with the protocol requirements; 2. No gender restriction; 3. Age: ≥18 and ≤75 years (Phase Ia); ≥18 years (Phase Ib); 4. Expected survival ≥3 months; 5. Locally advanced or metastatic esophageal squamous cell carcinoma, gastric cancer, colorectal cancer, or other solid tumors; 6. Agree to provide archived tumor tissue specimens or fresh tissue samples from primary or metastatic lesions obtained within 2 years; 7. Must have at least one measurable lesion as defined by RECIST v1.1; 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 9. Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0; 10. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%; 11. Organ function levels must meet the protocol-specified requirements; 12. Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (aPTT) ≤1.5 × upper limit of normal (ULN); 13. Urine protein ≤2+ or ≤1000 mg/24h; 14. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days prior to the start of treatment, with a negative serum pregnancy test result, and they must be non-lactating; all study participants (both male and female) must use adequate barrier contraception throughout the entire treatment period and for 7 months after the completion of treatment.
Exclusion criteria
1. Use of chemotherapy, biotherapy, immunotherapy, or other anti-tumor therapies within 4 weeks or 5 half-lives prior to the first dose; 2. History of severe cardiac disease; 3. QT interval prolongation, complete left bundle branch block, or third-degree atrioventricular block; 4. Active autoimmune diseases and inflammatory diseases; 5. Diagnosis of another malignant tumor within 5 years prior to the first dose; 6. Hypertension inadequately controlled by two antihypertensive agents; 7. History of interstitial lung disease (ILD) requiring corticosteroid therapy, or current ILD, or radiation pneumonitis of Grade ≥2; 8. Active central nervous system (CNS) metastases; 9. Subjects with a history of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient component of BL-ARC002; 10. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation; 11. Cumulative anthracycline dose \> 360 mg/m² from prior (neo)adjuvant anthracycline-based therapy; 12. Positive for human immunodeficiency virus (HIV) antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection; 13. Active infection requiring systemic therapy; 14. Participation in another clinical trial within 4 weeks prior to the first dose; 15. Pregnant or breastfeeding women; 16. Subjects with claustrophobia or inability to lie flat for the duration of required examinations due to various reasons; 17. Any other conditions that, in the investigator's judgment, make the subject unsuitable for participation in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 BL-ARC002. |
| 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 BL-ARC002. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-ARC002. |
| Cmax | Up to approximately 24 months | Cmax is defined as the maximum observed drug concentration in plasma after administration. |
| Tmax | Up to approximately 24 months | Tmax is defined as the time required to reach the maximum drug concentration in plasma following drug administration. |
| T1/2 | Up to approximately 24 months | T1/2 is defined as the time required for the plasma concentration of a drug to decrease by 50% during the elimination phase. |
| 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 | Clearance (CL) is the volume of plasma from which a drug is completely removed per unit time. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration prior to the next dose will be administered. |
| ADA (anti-drug antibody) | Up to approximately 24 months | Frequency of anti-BL-ARC002 antibody (ADA) will be investigated. |
| Radiation Characteristics | Up to approximately 24 months | Radiation characteristics refer to the comprehensive set of physical and biological parameters that describe the deposition, distribution, and biological consequences of ionizing radiation in clinical trials, encompassing both dosimetric metrics and associated toxicity profiles. |
| 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. |
Countries
China
Contacts
CONTACTSa Xiao, PHD
Outcome results
None listed