Trial Title:
A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT ID:
NCT05943795
Condition:
Non-small Cell Lung Adenocarcinoma
Squamous Cell Carcinoma of Lung
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Adenocarcinoma
Adenocarcinoma of Lung
Lung Neoplasms
Docetaxel
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
SI-B001
Description:
Administration by intravenous infusion
Arm group label:
Experimental group
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Administration by intravenous infusion
Arm group label:
Control group
Summary:
Main objectives: To evaluate the benefit of SI-B001+ docetaxel on overall survival (OS)
of bidotaxel. To evaluate the benefit of SI-B001+ Docetaxel over Docetaxel's
progression-free survival (PFS) based assessment. Secondary objectives: To evaluate the
investigator-evaluated progression-free survival (PFS) benefit of SI-B001+ Docetaxel
against docetaxel; To evaluate the difference of objective response rate (ORR), disease
control rate (DCR) and duration of response (DOR) between SI-B001+ docetaxel and
bidocetaxel. To evaluate the type, frequency and severity of adverse events (TEAE) and
drug-related adverse events (TRAE) during treatment with SI-B001+ docetaxel in comparison
with docetaxel. The pharmacokinetic (PK) characteristics of SI-B001 will be evaluated.
The immunogenicity of SI-B001 will be evaluated. Subject quality of life.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Sign the informed consent voluntarily and follow the program requirements;
2. No gender limitation;
3. Age ≥18 years and ≤80 years;
4. Expected survival time ≥3 months;
5. Histologically or cytologically confirmed, locally advanced or metastatic EGFR
wild-type, ALK wild-type, and other driver negative (AGA negative, including MET 14
exon jump mutation, ROS1 rearrangement, BRAF V600 mutation, NTRK fusion, RET
rearrangement, HER2 mutation, Patients with HER2 amplification (> 3.2 copies), KRAS
G12 mutation (e.g., G12C, G12D, G12V, etc.) negative), non-small cell lung cancer
(squamous cell carcinoma, adenocarcinoma), who only received anti-PD-1 /PD-L1
monoclonal antibody + platino-containing dimorphization and disease progression or
intolerance at the first line; Note: a. Platinum-containing chemotherapy (induction
chemotherapy, chemoradiotherapy and adjuvant chemotherapy) in multi-mode therapy for
locally advanced patients with disease progression during treatment or within 6
months after the last administration can be counted as first-line therapy. If no
treatment with anti-PD-1 /PD-L1 monoclonal antibody is received, the inclusion
criteria cannot be met. Inclusion criteria were met if maintenance therapy with
anti-PD-1 /PD-L1 monoclonal antibody and disease recurrence/progression occurred
within 6 months after the last administration of platinum-containing chemotherapy
drugs; b. For patients who need genetic testing or IHC testing and receive
platinum-containing diplination first, they should only receive platinum-containing
diplination at most in the first 2 cycles, and then add anti-PD-1 /PD-L1 monoclonal
antibody for combination therapy, which meets the inclusion criteria; Patients
receiving anti-PD-1 /PD-L1 monoclonal antibody and then sequential chemotherapy
drugs did not meet the inclusion criteria; c. Any change of medication during
front-line treatment shall be counted as an increase in the number of treatment
lines;
6. Subject shall agree to complete ctDNA test during the screening period, including:
EGFR, ALK, MET, ROS1, BRAF, NTRK, RET, HER2, KRAS and other genes detection and
complete data;
7. There must be at least one measurable lesion consistent with the RECIST v1.1
definition;
1. If there is only one measurable lesion, baseline imaging of the lesion should
not be performed until at least 14 days after biopsy if biopsy has been
performed;
2. If the target lesion at the site of previous radiotherapy is the only
measurable lesion, the investigator must provide imaging data before and after
showing significant progression of the lesion to confirm clear progression of
the lesion and at least 3 months after the end of radiotherapy;
8. Physical status score ECOG 0 or 1;
9. The toxicity of previous antitumor therapy has returned to class 1 as defined by
NCI-CTCAE v5.0 (alopecia, fatigue, hyperpigmentation, hypothyroidism stabilized by
hormone replacement therapy, grade 2 peripheral neurotoxicity after chemotherapy,
and other inclusion criteria excluded);
10. No serious cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. If blood transfusion, albumin, colony-stimulating factors, any cell growth factors,
and/or thrombocytophors are not permitted within 14 days prior to the initial use of
the study drug, organ function levels must meet the following requirements and meet
the following criteria:
1. Bone marrow function: absolute neutrophil count (ANC) ≥1.5×109/L, platelet
count ≥100×109/L, hemoglobin ≥90 g/L;
2. Liver function: total bilirubin TBIL≤1.5×ULN (total bilirubin ≤3×ULN in
subjects with Gilbert's syndrome or liver metastasis), AST and ALT ≤2.5×ULN in
subjects without liver metastasis, AST and ALT ≤5.0×ULN in patients with liver
metastasis, albumin ≥30 g/L;
3. Renal function: creatinine (Cr) ≤1.5×ULN, or creatinine clearance (Ccr) ≥50
mL/min (according to Cockcroft and Gault formula);
12. Coagulation function: International standardized ratio (INR) ≤1.5, and activated
partial thromboplastin time (APTT) ≤1.5×ULN;
13. Urinary protein ≤2+ or < 1000mg/24h;
14. A pregnancy test must be performed within 7 days before the start of treatment for
premenopausal women who are likely to have children, and the serum-pregnancy must be
negative and must be non-lactation; All enrolled patients (male or female) should
take adequate barrier contraception throughout the treatment cycle and for 6 months
after completion of treatment.
Exclusion Criteria:
1. Patients with previous use of docetaxel;
2. Patients with non-small cell lung cancer except lung squamous cell carcinoma and
lung adenocarcinoma confirmed by histological or cytological examination (excluding
patients with squamous cell carcinoma or adenocarcinoma combined with other types of
non-small cell lung cancer);
3. The gene sequencing report of previous tissue samples or ctDNA before signing the
informed consent, or the gene sequencing report of ctDNA during the screening period
indicated that there were positive MET 14 exon jump, positive ROS1 rearrangement,
positive BRAF V600 mutation, positive NTRK fusion, positive RET rearrangement, and
positive HER2 mutation. Patients with HER2 amplification (> 3.2 copies) and KRAS G12
mutation positive (e.g., G12C, G12D, G12V, etc.) should be excluded.
4. Used chemotherapy, biotherapy, immunotherapy, radical radiotherapy, major surgery,
extensive radiotherapy (more than 30% bone marrow radiotherapy or extensive
radiotherapy) within 4 weeks before the first dose or within 5 half-lives (whichever
is shorter), Anti-tumor therapy has been used within 2 weeks, such as palliative
radiotherapy (but it is allowed for bone lesions), small-molecule targeted therapy
(including small-molecule tyrosine kinase inhibitors), and modern Chinese medicine
preparations approved and marketed for anti-tumor therapy with NMPA;
5. The medical history of severe cardiac and cerebrovascular diseases in the previous
six months was screened, such as: symptomatic congestive heart failure (CHF) ≥2
(CTCAE v5.0) medical history, New York Heart Society (NYHA) ≥3 heart failure,
unstable angina pectoris, acute coronary syndrome, myocardial infarction,
cerebrovascular accident, transient ischemic attack, cerebral infarction, etc.;
6. Prolonged QT interval (male QTc > 450 msec or female QTc > 470 msec, QTc interval
calculated by Fridericia formula), complete left bundle branch block, degree III
atrioventricular block, frequent and uncontrolled arrhythmias: Such as atrial
fibrillation, atrial flutter, ventricular fibrillation, ventricular flutter
(transient atrial fibrillation, except for atrial flutter);
7. Active autoimmune diseases and inflammatory diseases, such as systemic lupus
erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis,
inflammatory bowel diseases, Hashimoto's thyroiditis, etc., except type I diabetes
mellitus, hypothyroidism that can be controlled by alternative therapy alone, and
skin diseases that do not require systemic treatment (e.g. Vitiligo, psoriasis);
8. Diagnosis of other malignancies within 5 years prior to initial administration, with
the exception of radically treated basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, and/or radically resected carcinoma in situ, which the
investigators considered acceptable for inclusion;
9. Hypertension poorly controlled by two antihypertensive drugs (systolic blood
pressure > 150 mmHg or diastolic blood pressure > 100 mmHg);
10. Patients with past and present clinical manifestations or high risk factors of
interstitial lung disease (ILD), drug-related pneumonia, radiation pneumonia, severe
impairment of lung function or suspected interstitial lung disease;
11. Patients with central nervous system (CNS) metastasis and/or cancerous meningitis
(meningeal metastasis) and/or spinal cord compression. But have received brain
metastases (radiation or surgery; Patients with stable BMS who had stopped
radiotherapy or surgery 28 days before the first dose were enrolled. Patients with
cancerous meningitis (meningeal metastasis) were excluded even after treatment and
judged to be stable, and patients with cerebral edema and mannitol
prophylaxis/treatment were excluded even if asymptomatic. The definition of
stability should meet the following four requirements:
1. The seizure-free state persists for > 12 weeks with or without the use of
antiepileptic drugs;
2. glucocorticoids are not required;
3. MRI results during the screening period showed stable imaging status compared
with previous MRI results of the subjects;
4. asymptomatic and stable for more than 1 month after treatment;
12. Patients who have a history of allergy to recombinant humanized antibody or human
and mouse chimeric antibody or to SI-B001 and any excipient components of the
chemotherapy drugs used in this study;
13. History of autologous or allogeneic stem cell transplantation or organ
transplantation;
14. Positive human immunodeficiency virus antibodies (HIVAb), active hepatitis B virus
infection (HBV-DNA > 103 copies/ml) or hepatitis C virus infection (HCV-RNA > lower
limit of centre detection);
15. Severe infections (CTCAE > Grade 2), such as severe pneumonia, bacteremia, sepsis,
tuberculosis, etc., occurred within 4 weeks prior to the first use of the study
drug; There was active pulmonary inflammation during screening;
16. Patients with a large amount of serous effusion, or with symptoms of serous
effusion, or poorly controlled serous effusion (poorly controlled is defined as two
or more times of puncture and drainage in a month);
17. Contraindicated fluid replenishment with superior vena cava syndrome;
18. Received other investigational drugs or treatments within 4 weeks prior to initial
dosing;
19. A history of severe neurological or mental illness, including but not limited to:
dementia, depression, seizures, bipolar disorder, etc.;
20. Imaging examination indicated that the tumor had invaded or wrapped the great
vessels of the chest (such as the pulmonary trunk, aorta trunk, pulmonary veins,
etc.);
21. Severe and unhealed wounds, sores or fractures within 4 weeks prior to signing the
notice;
22. Coughed up or coughed up (defined as coughing up or coughed up ≥1 teaspoon of blood
or small blood clots or coughed up blood without sputum) within 4 weeks before
signing the notification, but did not exclude blood in the sputum;
23. Severe infusion reaction to antibody therapy in the past (CTCAE grade ≥3);
24. Subjects with clinically significant bleeding or significant bleeding tendency
within 4 weeks prior to signing the information, such as gastrointestinal bleeding,
hemorrhagic gastric ulcer, vasculitis, etc.;
25. History of intestinal obstruction, inflammatory bowel disease or extensive bowel
resection, or presence of Crohn's disease, ulcerative colitis, or chronic diarrhea;
26. Subjects who plan to receive live vaccine or receive live vaccine within 30 days
prior to initial administration;
27. Other conditions associated with participation in this clinical trial were not
considered appropriate by the investigators.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510000
Country:
China
Status:
Recruiting
Contact:
Last name:
XuZhi Pan
Phone:
020-87343009
Email:
llwyh@sysucc.org.cn
Investigator:
Last name:
Li Zhang, PHD
Email:
Principal Investigator
Start date:
July 14, 2023
Completion date:
July 2026
Lead sponsor:
Agency:
Sichuan Baili Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Sichuan Baili Pharmaceutical Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05943795
