Solid Tumors
Conditions
Brief summary
This study is an open-label, multicenter, dose-escalation and expansion, non-randomized Phase I clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy of BL-ARC002 for 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 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 comply with the protocol requirements; 2. No gender restrictions; 3. Age: ≥18 and ≤75 years (Phase Ia); ≥18 years (Phase Ib); 4. Expected survival time ≥3 months; 5. Histopathologically and/or cytologically confirmed locally advanced or metastatic solid tumors that have failed standard treatment; 6. Agree to provide archived tumor tissue specimens or fresh tissue samples from the primary or metastatic lesions within the past 2 years; 7. Must have at least one measurable lesion as defined by RECIST v1.1; 8. Eastern Cooperative Oncology Group performance status of 0 or 1; 9. Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0; 10. No severe cardiac dysfunction, with left ventricular ejection fraction ≥50%; 11. Organ function levels must meet the required criteria; 12. Coagulation function: International normalized ratio ≤1.5 and activated partial thromboplastin time ≤1.5 × upper limit of normal; 13. Urine protein ≤2+ or ≤1000 mg/24 hours; 14. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, with serum pregnancy test being negative, and they must not be breastfeeding; all enrolled patients (regardless of sex) must practice adequate barrier contraception throughout the entire treatment period and for 6 months after treatment completion.
Exclusion criteria
1. Use of chemotherapy, biotherapy, immunotherapy, etc., within 4 weeks or 5 half-lives prior to the first dose; 2. History of serious heart 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 malignancy within 5 years prior to the first dose; 6. Hypertension inadequately controlled by two antihypertensive medications; 7. History of ILD requiring steroid therapy, current ILD, or ≥ Grade 2 radiation pneumonitis; 8. Active symptoms of central nervous system metastasis; 9. History of allergy to recombinant humanized 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 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. Pregnancy or breastfeeding; 16. Study participants with claustrophobia or any condition preventing them from lying still to complete examinations; 17. Other conditions deemed by the investigator to make the participant unsuitable for this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 BL-ARC002. |
| 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 |
|---|---|---|
| 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. |
| 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 | Maximum serum concentration (Cmax) of BL-ARC002 will be investigated. |
| Tmax | Up to approximately 24 months | Time to maximum serum concentration (Tmax) of BL-ARC002 will be investigated. |
| T1/2 | Up to approximately 24 months | Half-life (T1/2) of BL-ARC002 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. |
| 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 \[PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]). |
| CL (Clearance) | Up to approximately 24 months | CL in the serum of BL-ARC002 per unit of time will be investigated. |
| 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. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration of BL-ARC002 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. |
Countries
China
Contacts
CONTACTSa Xiao, PHD
Outcome results
None listed