A Study of BL-B01D1 in Patients With Locally Advanced or Metastatic Urological Tumors and Other Solid Tumors
Study Details
Study Description
Brief Summary
In phase Ia study, the safety and tolerability of BL-B01D1 in patients with locally advanced or metastatic urinary tumors and other solid tumors will be investigated to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) of BL-B01D1.
In phase Ib study, the safety and tolerability of BL-B01D1 at the phase Ia recommended dose will be further investigated, and recommended phase II dose (RP2D) for phase II clinical studies will be determined.
In addition, the preliminary efficacy, pharmacokinetic characteristics, and immunogenicity of BL-B01D1 in patients with locally advanced or metastatic urinary tumors and other solid tumors will be evaluated.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Study treatment Participants receive BL-B01D1 as intravenous infusion for the first cycle (4 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons. |
Drug: BL-B01D1
Administration by intravenous infusion
|
Outcome Measures
Primary Outcome Measures
- Phase Ia: Dose limiting toxicity (DLT) [Up to 28 days after the first dose of BL-B01D1]
DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle (28 days) 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 28 days after the first dose of BL-B01D1]
MTD is defined as the highest dose level at which no more than 1 in 9 participants experienced a DLT during the first cycle (within 28 days of the first administration
- Phase Ib: Recommended Phase II Dose (RP2D) [Up to 28 days after the first dose of BL-B01D1]
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-B01D1
Secondary Outcome Measures
- 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-B01D1 . The type, frequency and severity of TEAE will be evaluated during the treatment of BL-B01D1 .
- Cmax [Up to 28 days after the first dose of BL-B01D1]
Maximum serum concentration (Cmax) of BL-B01D1 will be investigated.
- Tmax [Up to 28 days after the first dose of BL-B01D1]
Time to maximum serum concentration (Tmax) of BL-B01D1 will be investigated.
- T1/2 [Up to 28 days after the first dose of BL-B01D1]
Half-life (T1/2) of BL-B01D1 will be investigated.
- AUC0-t [Up to 28 days after the first dose of BL-B01D1]
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 28 days after the first dose of BL-B01D1]
CL in the serum of BL-B01D1 per unit of time will be investigated.
- Ctrough [Up to 28 days after the first dose of BL-B01D1]
Ctough is defined as the lowest serum concentration of BL-B01D1 prior to the next dose will be administered.
- ADA (anti-drug antibody) [Up to approximately 24 months]
Incidence of ADA of BL-B01D1 will be evaluated.
- ADA (anti-drug antibody) [Up to approximately 24 months]
Titer of ADA of BL-B01D1 will be evaluated.
- Nab (neutralizing antibody) [Up to approximately 24 months]
Incidence of Nab of BL-B01D1 will be evaluated.
- Nab (neutralizing antibody) [Up to approximately 24 months]
Titer of Nab of BL-B01D1 will be evaluated.
- 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.
- 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]).
- 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.
- Progression-free Survival (PFS) [Up to approximately 24 months]
The PFS is defined as the time from the participant's first dose of BL-B01D1 to the first date of either disease progression or death, whichever occurs first.
- Overall Survival (OS) [Up to approximately 24 months]
The OS is defined as the time from randomization to death (from any cause).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participants must sign the informed consent form voluntarily and follow the plan requirements;
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No gender limit;
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Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib);
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Expected survival time ≥ 3 months;
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Locally advanced or metastatic tumors of the urinary system and other solid tumors confirmed by histopathology and/or cytology, which are incurable or currently without standard treatment. Intolerance refers to the occurrence of grade 3-4 adverse reactions after a patient has received standard treatment, and the patient refuses to continue the original treatment;
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Agree to provide archived tumor tissue specimens (10 unstained sections (anti-extraction) surgical specimens (thickness 4-5μm)) or fresh tissue samples from primary or metastatic lesions within 3 years. If patients cannot provide such specimens, they can be included in the group after the judgment of the investigator if other inclusion criteria are met;
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Participants must have at least one measurable lesion that meets the definition of RECIST v1.1;
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Physical fitness score ECOG 0 or 1 point;
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The toxicity of previous anti-tumor treatments has been restored to NCI-CTCAE v5.0 definition ≤ 1 (except for hair loss);
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No serious cardiac dysfunction, left ventricular ejection fraction (LVEF) ≥50%;
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The organ function must meet the following requirements and standards: a) Bone marrow function: absolute neutrophil count (ANC) ≥1.5×109/L, platelet count ≥75×109/L, hemoglobin ≥90 g/L; B) Liver function: total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5 ULN for participants without liver metastasis, AST and ALT ≤5.0 ULN for liver metastases; c) Kidney function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to the Cockcroft and Gault formula);
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Coagulation function: International normalized ratio (INR)≤1.5×ULN, and activated partial thromboplastin time (APTT)≤1.5ULN;
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For premenopausal women with childbearing potential, a pregnancy test must be taken within 7 days prior to the start of treatment. Serum or urine pregnancy must be negative and must be non-lactating; all participants (regardless of male or female) in the group should be treated throughout the treatment. Adequate barrier contraceptive measures should be taken during the treatment and 6 months after the treatment.
Exclusion Criteria:
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Prior use of antibody-coupled drugs (ADC);
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Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other anti-tumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration; oral fluorouracil-like drugs such as S-1, capecitabine, or palliative radiotherapy within 2weeks prior to the first administration;
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Have a history of serious cardiovascular and cerebrovascular diseases, including but not limited to:
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Have serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias and ⅲ degree ATrioventricular block requiring clinical intervention;
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QT interval was prolonged in resting state (QTc > 450 msec for men or 470 msec for women);
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Myocardial infarction, unstable angina, cardiac angioplasty or stent implantation, coronary artery/peripheral artery bypass graft, Class ⅲ or ⅳ congestive heart failure, cerebrovascular accident, or transient ischemic attack within 6 months prior to the first administration;
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Active autoimmune diseases and inflammatory diseases, such as: systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, etc., except for type I diabetes, hypothyroidism that can be controlled only by alternative treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis);
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Other malignant tumors were diagnosed within 2 years prior to the first administration with the following exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after radical resection;
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Participants have grade 3 lung disease defined according to NCI-CTCAE v5.0, or a history of interstitial lung disease (ILD);
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Symptoms of active central nervous system metastasis. However, participants with stable brain metastasis can be included. Stable is defined as:
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The seizureless state lasted for > 3 months with or without antiepileptic drugs;
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Central nervous system (CNS) metastases and/or cancerous meningitis. Subjects who have been treated with BMS who have been stable for at least 3 months, who have no disease progression determined by imaging within 28 days prior to initial treatment with the study drug, and who have returned all neurological symptoms to grade ≤1 (CTCAE5.0) or baseline (other than signs or symptoms associated with CNS treatment) for at least 2 weeks, Patients with no evidence of new or expanded BMS and a prednisone treatment dose of 20mg/ day or less (or equivalent) within 7 days prior to initial treatment with the study drug were eligible for inclusion in the study. Cancerous meningitis, whether clinically stable or not, should be excluded;
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Participants who have a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL-B01D1;
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Participants have a history of autologous or allogeneic stem cell transplantation（Allo-HSCT);
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In the adjuvant (or neoadjuvant) treatment of anthracyclines, the cumulative dose of anthracyclines is> 360 mg/m2;
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Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number> the lower limit of detection) or active hepatitis C virus infection(HCV antibody positive and HCV-RNA > the lower limit of detection);
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Participants with active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc;
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Other conditions that the investigator believes that it is not suitable for participating in this clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Cancer Hospital | Beijing | Beijing | China |
Sponsors and Collaborators
- Sichuan Baili Pharmaceutical Co., Ltd.
- SystImmune Inc.
Investigators
- Principal Investigator: Jun Guo, PHD, Peking University Cancer Hospital & Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BL-B01D1-102