Squamous Non-small-cell Lung Cancer
Conditions
Brief summary
This trial is a registrational Phase II/III randomized, open-label, multicenter study designed to evaluate the efficacy and safety of BL-B01D1 in combination with PD-1/VEGF bispecific antibody in first-line patients with locally advanced or metastatic squamous non-small cell lung cancer.
Detailed description
The entire study consists of two stages, Phase II and Phase III, both of which are randomized, open-label studies.
Interventions
DRUGBL-B01D1
Administration by intravenous infusion for a cycle of 3 weeks.
Administration by intravenous infusion for a cycle of 3 weeks.
DRUGPaclitaxel
Administration by intravenous infusion for a cycle of 3 weeks.
DRUGCarboplatin
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
RANDOMIZED
Intervention model
PARALLEL
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. Age ≥18 years; 3. Expected survival time ≥3 months; 4. Patients with locally advanced or metastatic squamous non-small cell lung cancer; 5. Agree to provide tumor tissue samples obtained at or after the diagnosis of locally advanced or metastatic disease; 6. Must have at least one measurable lesion as defined by RECIST v1.1; 7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 8. Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0; 9. No severe cardiac dysfunction, with left ventricular ejection fraction ≥50%; 10. Organ function levels must meet the specified requirements; 11. Urinary protein ≤1+ or \<1000 mg/24h; 12. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, with serum pregnancy test excluding pregnancy, and patients must be non-lactating; all enrolled patients (regardless of male or female) must take adequate barrier contraceptive measures throughout the entire treatment period and for 7 months after the end of treatment.
Exclusion criteria
1. Prior histological or cytological evidence of small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma components; 2. Indications of the presence of EGFR-sensitive mutations, among others; 3. Patients who have received prior systemic therapy; 4. Prior treatment with agents targeting the mechanism of tumor immune action; 5. Prior treatment with ADC drugs that use topoisomerase I inhibitors as the toxin, among others; 6. Receipt of radical radiotherapy, major surgery, or large-field radiotherapy within 4 weeks before study randomization; 7. History of severe heart disease or cerebrovascular disease; 8. Receipt of long-term systemic corticosteroid therapy (e.g., prednisone \>10 mg/day) before the first dose; 9. Active autoimmune diseases and inflammatory diseases requiring systemic treatment within 2 years; 10. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; 11. Prolonged QTc interval, complete left bundle branch block, among others; 12. Diagnosis of active malignancy within 3 years before study randomization; 13. Hypertension inadequately controlled by two antihypertensive medications; 14. Patients with poorly controlled blood glucose levels; 15. History of ILD requiring steroid therapy, current ILD, or grade ≥2 radiation pneumonitis, among others; 16. Pulmonary diseases leading to clinically severe impairment of respiratory function; 17. Patients with active central nervous system metastases; 18. Severe infection occurring within 4 weeks before study randomization; 19. Presence of large serous cavity effusions or symptomatic serous cavity effusions, among others; 20. Imaging findings indicating tumor invasion or encasement of the abdomen, chest, etc.; 21. Severe non-healing wounds, ulcers, or fractures within 4 weeks before signing informed consent; 22. Trial participants with clinically significant bleeding or a significant bleeding tendency within 4 weeks prior to signing informed consent; 23. Patients with inflammatory bowel disease, history of extensive bowel resection, history of immune enteritis, intestinal obstruction, or chronic diarrhea, among others; 24. History of allergy to recombinant humanized antibodies or hypersensitivity to any excipient of BL-B01D1; 25. History of autologous or allogeneic stem cell transplantation; 26. Positive for human immunodeficiency virus antibody, active hepatitis B virus infection, or hepatitis C virus infection; 27. History of severe neurological or psychiatric disorders; 28. Receipt of other unapproved clinical study drugs or treatments within 4 weeks before study randomization; 29. Trial participants planning to receive or having received live vaccines within 28 days before study randomization; 30. Other conditions deemed by the investigator as unsuitable for participation in this clinical trial due to complications or other circumstances.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase II: Investigator-assessed Progression-free Survival (PFS) | Up to approximately 24 months | Investigator-assessed progression-free survival (PFS) per RECIST v1.1 is defined as the time from treatment initiation until the first documented disease progression according to RECIST v1.1 criteria, or death from any cause, whichever occurs first, as determined by the local treating investigator. |
| Phase III: BICR-assessed Progression-free Survival (PFS) | Up to approximately 24 months | Progression-free survival (PFS) as assessed by BICR is defined as the time between the date subjects were randomized and the first observation of disease progression (based on BICR's image-based assessment) or death. |
| Phase II: Investigator-assessed Objective Response Rate (ORR) | Up to approximately 24 months | Objective response rate (ORR) is defined as the number of CR and PR in the treatment and control groups divided by the number of that group in the full analysis set (FAS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase II: Drug-Drug Interaction (DDI) | Up to approximately 24 months | Drug-Drug Interaction (DDI) is a situation in which one drug affects the activity, metabolism, or toxicity of another drug when they are administered concurrently (or within a short time interval). |
| Phase III: Overall Survival (OS) | Up to approximately 24 months | Overall survival (OS) is defined as the time between the day the subject is randomized and the subject's death. |
| Phase II/III: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. |
| Phase II/III: Progression-free Survival (PFS) | Up to approximately 24 months | Progression-free Survival (PFS) is defined as the time from randomization or start of treatment until the first documented evidence of disease progression or death from any cause, whichever occurs first. |
| Phase II/III: Objective Response Rate (ORR) | Up to approximately 24 months | Objective response rate (ORR) is defined as the number of CR and PR in the treatment and control groups divided by the number of that group in the full analysis set (FAS). |
| Phase II/III: Disease Control Rate (DCR) | Up to approximately 24 months | Disease Control Rate (DCR) : Percentage of all randomized subjects who rated the best overall response (BOR) as complete response (CR), partial response (PR), and disease stabilization (SD) according to RECIST 1.1 criteria. |
| Phase II/III: Duration of Response (DOR) | Up to approximately 24 months | Duration of Response (DOR) : defined as the period from the date when tumor response is first recorded to the date when objective tumor progression is first recorded or the date of death. |
| Phase II/III: Cmax | Up to approximately 24 months | Cmax is defined as the maximum observed drug concentration in plasma after administration. |
| Phase II/III: Tmax | Up to approximately 24 months | Tmax is defined as the time required to reach the maximum drug concentration in plasma following drug administration. |
| Phase II/III: 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. |
| Phase II/III: 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 II/III: Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration prior to the next dose will be administered. |
| Phase II/III: CL (Clearance) | Up to approximately 24 months | Clearance (CL) is the volume of plasma from which a drug is completely removed per unit time. |
| Phase II/III: Anti-drug Antibody (ADA) | Up to approximately 24 months | Anti-drug Antibody (ADA) refers to endogenous antibodies generated in subjects that specifically bind to the investigational drug. |
| Phase II/III: Neutralizing Antibody(NAb) | Up to approximately 24 months | Frequency of anti-BL-B01D1 neutralizing antibodies will be investigated. |
Countries
China
Contacts
CONTACTSa Xiao, PHD
Outcome results
None listed