Solid Tumor
Conditions
Brief summary
This study is an open, multicenter, dose-escalation and expansion-enrollment, nonrandomized phase I clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of BL-M08D1 for injection in locally advanced or metastatic solid tumors.
Interventions
DRUGBL-M08D1
Administration by intravenous infusion for a cycle of 3 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. Sign the informed consent form voluntarily and follow the protocol requirements; 2. Gender is not limited; 3. Age: ≥18 years old and ≤75 years old (phase Ia); ≥18 years old (phase Ib); 4. Expected survival time ≥3 months; 5. Locally advanced or metastatic solid tumors confirmed by histopathology and/or cytology that are incurable or currently have no standard treatment; 6. Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 2 years; 7. At least one measurable lesion meeting the RECIST v1.1 definition was required; 8. ECOG 0 or 1; 9. The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0; 10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%; 11. No blood transfusion, no use of cell growth factors and/or platelet-raising drugs within 14 days before screening, and the organ function level must meet the requirements; 12. Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5ULN; 13. Urinary 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 the patient must not be lactating; All enrolled patients (regardless of male or female) should use adequate barrier contraception during the whole treatment cycle and for 6 months after the end of treatment; 15. Subjects were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.
Exclusion criteria
1. Chemotherapy, biological therapy and other anti-tumor therapies have been used within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil; 2. History of severe heart disease; 3. QT prolongation, complete left bundle branch block, III degree atrioventricular block; 4. Active autoimmune and inflammatory diseases; 5. Other malignant tumors diagnosed within 5 years before the first dose; 6. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg); 7. History of ILD requiring steroid therapy or current ILD or ≥ grade 2 radiation pneumonitis; 8. Complicated with pulmonary diseases leading to clinically severe respiratory function impairment; 9. Had symptoms of active central nervous system metastasis; 10. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of the ingredients of BL-M08D1; 11. Received previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT); 12. Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection; 13. Active infection requiring systemic therapy within 4 weeks before the first dose of study drug; 14. Pleural, abdominal, pelvic or pericardial effusion requiring drainage and/or with symptoms within 4 weeks before the first dose of study drug; 15. Received another trial drug 4 weeks or 5 half-lives before the first dose; 16. Pregnant or lactating women; 17. The investigator did not consider it appropriate to apply other criteria for participation in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ia: Dose limiting toxicity (DLT) | Up to 21 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 21 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-M08D1. |
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-M08D1 . The type, frequency and severity of TEAE will be evaluated during the treatment of BL-M08D1. |
| Cmax | Up to approximately 24 months | Maximum serum concentration (Cmax) of BL-M08D1 will be investigated. |
| Tmax | Up to approximately 24 months | Time to maximum serum concentration (Tmax) of BL-M08D1 will be investigated. |
| T1/2 | Up to approximately 24 months | Half-life (T1/2) of BL-M08D1 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 BL-M08D1 per unit of time will be investigated. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration of BL-M08D1 prior to the next dose will be administered. |
| ADA (anti-drug antibody) | Up to approximately 24 months | Frequency of anti-BL-M08D1 antibody (ADA) 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. |
Countries
China
Contacts
CONTACTSa Xiao, PHD
Outcome results
None listed