Non Small Cell Lung Cancer, Solid Tumor
Conditions
Brief summary
This study is an open, multicenter, non-randomized phase I clinical trial to evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy of BL-M24D1 in patients with locally advanced or metastatic non-small cell lung cancer and other solid tumors.
Detailed description
The study consists of two phases: a dose escalation phase (Phase Ia) and a dose expansion phase (Phase Ib).
Interventions
DRUGBL-M24D1
Administration by intravenous infusion for a cycle of 2 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 unrestricted; 3. Age: ≥18 years and ≤75 years (Phase Ia); ≥18 years (Phase Ib); 4. Expected survival time ≥3 months; 5. Locally advanced or metastatic non-small cell lung cancer and other 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 they 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 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. Poorly controlled blood glucose; 8. Unstable thrombotic events requiring therapeutic intervention within 6 months prior to the first dose; 9. Lung diseases graded ≥3 according to CTCAE v5.0; 10. Symptoms of active central nervous system metastasis; 11. History of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient of BL-M24D1; 12. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation; 13. Cumulative dose of anthracyclines \>360 mg/m² in previous (neo)adjuvant anthracycline therapy; 14. Positive human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection; 15. History of interstitial lung disease requiring hormonal treatment, or current ILD; 16. Active infection requiring systemic treatment within 4 weeks prior to the first investigational drug dose; 17. Pleural, peritoneal, pelvic, or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first investigational drug dose; 18. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks prior to the first investigational drug dose; 19. Participation in another clinical trial within 4 weeks prior to the first dose; 20. Pregnant or lactating women; 21. Other conditions 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 28 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 28 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-M24D1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| T1/2 | Up to approximately 24 months | Half-life (T1/2) of BL-M24D1 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-M24D1 per unit of time will be investigated. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration of BL-M24D1 prior to the next dose will be administered. |
| 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-M24D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-M24D1. |
| 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. |
| ADA (anti-drug antibody) | Up to approximately 24 months | Frequency of anti-BL-M24D1 antibody (ADA) will be investigated. |
| Cmax | Up to approximately 24 months | Maximum serum concentration (Cmax) of BL-M24D1 will be investigated. |
| Tmax | Up to approximately 24 months | Time to maximum serum concentration (Tmax) of BL-M24D1 will be investigated. |
Countries
China
Contacts
Primary ContactSa Xiao, PHD
Outcome results
None listed