Trial Title:
A Study of SI-B001+SI-B003± Chemotherapy in the Treatment of Locally Advanced or Metastatic Non-small Cell Lung Cancer
NCT ID:
NCT05949606
Condition:
Non-small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
SI-B001
Description:
Administration by intravenous infusion
Arm group label:
Study treatment
Intervention type:
Drug
Intervention name:
SI-B003
Description:
Administration by intravenous infusion
Arm group label:
Study treatment
Summary:
Phase Ib: To observe the safety and tolerability of the combination of SI-B001 and
SI-B003, and to determine the recommended dose of phase II clinical study (RP2D) in the
indication of locally advanced or metastatic non-small cell lung cancer. Phase II: To
evaluate the efficacy of SI-B001+SI-B003 combination with or without chemotherapy in
patients with locally advanced or metastatic non-small cell lung cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Voluntarily sign the informed consent and follow the requirements of the protocol;
2. No gender limit;
3. Age ≥18 years old and ≤75 years old;
4. expected survival time ≥3 months;
5. Participants must consent to complete ctDNA testing during the screening period,
including: EGFR, ALK, MET, ROS1, BRAF, NTRK, RET, HER2, KRAS and other genes
detection and complete data;
6. Histologically or cytologically confirmed locally advanced or metastatic non-small
cell lung cancer; Stage Ib: locally advanced or metastatic non-small-cell lung
cancer with negative driver genes (AGA-negative, including ALK fusion, MET exon 14
skipping mutation, ROS1 rearrangement, BRAF V600 mutation, NTRK fusion, and RET
rearrangement) after failure of standard therapy;
Phase II:
Cohort_A: Previously untreated, locally advanced or metastatic non-small cell lung
cancer patients with wild-type EGFR, wild-type ALK, and other driver genes negative
(AGA negative, including MET exon 14 skipping mutation, ROS1 rearrangement, BRAF
V600 mutation, NTRK fusion, and RET rearrangement negative); Cohort_B: Previously
untreated patients with locally advanced or metastatic EGFRmut non-small cell lung
cancer who had failed EGFR TKI therapy and had not received systemic chemotherapy.
Note: a. Patients were eligible if they were treated directly with third-generation
EGFR TKI, or if they were treated with first-generation or second-generation EGFR
TKI before progression to third-generation TKI; b. If the patient has progressed
after the first and second generation EGFR TKI treatment, but there is no indication
for the third generation EGFR TKI treatment (no EGFR T790M mutation), the third
generation EGFR TKI treatment is not required;
7. Consent to provide archived tumor tissue samples or fresh tissue samples of primary
or metastatic lesions; Phase Ib: participants could be enrolled if they could not
provide tumor tissue samples if they met other inclusion and exclusion criteria.
Stage II: PD-L1TPS test report (DAKO 22C3 antibody) of tumor tissue samples is
required; If no relevant examination report is available, patients must provide a
tumor tissue sample or fresh tissue sample (FFPE block or approximately 10-12 white
slides with a size of 5μm) from the primary or metastatic tumor within 2 years for
PD-L1 TPS, EGFR, or HER3 protein expression level detection.
8. At least one measurable lesion meeting the RECIST v1.1 definition was required.
9. Performance status score: ECOG ≤1;
10. Toxicity from previous antineochemical therapy has returned to grade 1 or less as
defined by NCI-CTCAE v5.0 (asymptomatic laboratory abnormalities such as elevated
ALP, hyperuricemia, elevated serum amylase/lipase, and elevated blood glucose were
considered by the investigator, and toxicity with no safety risk was judged by the
investigator; Except for alopecia, grade 2 peripheral neurotoxicity, and
hypothyroidism stable with hormone replacement therapy).
11. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
12. The level of organ function must meet the following requirements and meet the
following standards:
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 ≤1.5×ULN (total bilirubin ≤3×ULN in subjects
with Gilbert's syndrome and liver metastasis), AST and ALT ≤3×ULN in subjects
without liver metastasis, AST and ALT ≤5.0×ULN in subjects with liver
metastasis;
3. Renal function: creatinine (Cr) ≤1.5×ULN, or creatinine clearance (Ccr) ≥50
mL/min (according to Cockcroft and Gault formula).
13. Coagulation function: international normalized ratio (INR) ≤1.5 and activated
partial thromboplastin time (APTT) ≤1.5×ULN;
14. Urine protein ≤1+ or ≤1000mg/24h;
15. Female subjects of childbearing potential or male subjects with a fertile partner
must use highly effective contraception from 7 days before the first dose until 24
weeks after the dose. Female subjects of childbearing potential had to have a
negative serum pregnancy test within 7 days before the first dose.
Exclusion Criteria:
1. For stage Ib patients, patients with non-small-cell lung cancer with ALK fusion, MET
exon 14 skipping mutation, ROS1 rearrangement, BRAF V600 mutation, NTRK fusion, or
RET rearrangement on previous sequencing reports of tissue samples or ctDNA before
informed consent were excluded; For phase II Cohort_A: Genetic sequencing reports
from prior tissue samples or ctDNA before signing informed consent, or screening
ctDNA suggesting the following genetic alterations: Patients with ALK fusion, MET
exon 14 skipping mutation, ROS1 rearrangement, BRAF V600 mutation, NTRK fusion, or
RET rearrangement were excluded.
2. Phase II patients were excluded from the study if any of the following conditions
occurred:
1. patients suitable for local treatment and willing to receive local treatment;
2. received systemic chemotherapy, but not chemotherapy for locally advanced
disease as part of multimodal therapy (this treatment must have been completed
more than 6 months after the first dose of trial medication; The above
chemotherapy includes induction chemotherapy, concurrent chemoradiotherapy and
adjuvant chemotherapy).
3. Clinically symptomatic parenchymal or leptomeningeal metastases that were judged by
the investigator to be ineligible for enrollment. Patients with central nervous
system (CNS) metastases and/or carcinomatous meningitis (meningeal metastases)
and/or spinal cord compression. Patients who had received treatment for brain
metastases (radiotherapy or surgery; Patients who had stopped radiotherapy and
surgery 28 days before the first dose) and stable brain metastases were eligible.
Patients with cancerous meningitis (meningeal metastasis) were excluded even if they
were treated and judged to be stable, and patients with brain edema and treated with
mannitol were excluded even if they were judged to be asymptomatic. Stability is
defined as meeting the following four criteria:
1. seizure-free status for > 12 weeks with or without antiepileptic medication;
2. no need for corticosteroids;
3. screening MRI results, which showed a stable imaging state compared to the
subjects' previous MRI results;
4. stable and asymptomatic for more than one month after treatment;
4. Participants who participated in any other clinical trial within 4 weeks before the
study dose (whichever was the last dose);
5. Chemotherapy, biotherapy, immunotherapy, definitive radiotherapy, major surgery, or
large area radiotherapy (more than 30% bone marrow area or too large area
irradiation) administered within 4 weeks or 5 half-lives prior to the first dose,
whichever is shorter; Anti-tumor therapy such as palliative radiotherapy within 2
weeks (but palliative radiotherapy for bone lesions is allowed), small molecule
targeted therapy (including small molecule tyrosine kinase inhibitors), and modern
traditional Chinese medicine preparations approved by NMPA for anti-tumor therapy;
6. Major surgery (investigator-defined) within 4 weeks before the first dose;
7. Systemic corticosteroids (> 10mg/ day of prednisone, or other corticosteroids
equivalent) or immunosuppressive agents are required within 2 weeks before the study
administration; Exceptions include inhaled or topical administration of steroids or
physiological replacement doses of steroids for adrenal insufficiency;
8. Pulmonary disease grade ≥3 according to NCI-CTCAE v5.0; Patients with existing or a
history of interstitial lung disease (ILD);
9. Have active infection requiring intravenous anti-infective therapy;
10. Prior immunotherapy with grade ≥3 irAE or grade ≥2 immune-related myocarditis;
11. Administration of live attenuated vaccine within 4 weeks before the first dose of
study drug;
12. Use of immunomodulatory drugs, including but not limited to thymosin, interleukin-2,
interferon, etc., within 14 days before the first use of the study drug;
13. Patients at risk for active autoimmune disease, or with a history of autoimmune
disease, Including but not limited to Crohn's disease, ulcerative colitis, systemic
lupus erythematosus, sarcoidosis, Wegener syndrome, autoimmune hepatitis, systemic
sclerosis, Hashimoto's thyroiditis, autoimmune vasculitis, autoimmune neuropathy
(Guillain-Barre syndrome), etc. Exceptions were type I diabetes, hypothyroidism that
was stable with hormone-replacement therapy (including that due to autoimmune
thyroid disease), psoriasis or vitiligo that did not require systemic therapy, and
hypothyroidism that was stable with hormone-replacement therapy.
14. Patients with other malignant tumors within 5 years before the first drug
administration, except those who have been cured skin squamous cell carcinoma, basal
cell carcinoma, superficial bladder cancer, prostate/cervix/breast cancer in situ
and other researchers think can be enrolled;
15. Human immunodeficiency virus antibody (HIV Ab) positive, active tuberculosis, active
hepatitis B virus infection (HBsAg positive or HBcAb positive and HBV-DNA copy
number > 500IU/ml) or hepatitis C virus infection (HCV antibody positive and HCV-RNA
> central detection limit);
16. Hypertension poorly controlled by medication (systolic blood pressure > 150 mmHg
or diastolic blood pressure > 100 mmHg);
17. Has a history of severe cardiovascular and cerebrovascular diseases, including but
not limited to:
1. severe cardiac rhythm or conduction abnormalities, such as ventricular
arrhythmias or Ⅲ degree atrioventricular block requiring clinical intervention;
2. prolonged QT interval at rest (QTc > 450 msec in men or QTc > 470 msec in
women); Acute coronary syndrome, congestive heart failure, aortic dissection,
stroke, or other grade 3 or higher cardiovascular and cerebrovascular events
occurred within 6 months before the first dose;
3. patients with New York Heart Association (NYHA) functional class ≥II heart
failure;
18. Previous history of allogeneic stem cell, bone marrow or organ transplantation;
19. Patients with a history of allergy to recombinant humanized antibodies or to any of
the excipients of SI-B001 or SI-B003;
20. A history of autologous or allogeneic stem cell transplantation;
21. Pregnant or lactating women;
22. Other conditions for participation in the trial were not considered appropriate by
the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai Pulmonary Hospital
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Caicun Zhou, PHD
Investigator:
Last name:
Caicun Zhou, PHD
Email:
Principal Investigator
Start date:
October 30, 2023
Completion date:
November 2025
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/NCT05949606
