Clinical trial NCT05020457: SI-B001 Combined With Chemotherapy in the Treatment of EGFR/ALK WT Recurrent or Metastatic NSCLC.
Official title: A Phase II Clinical Study to Evaluate the Efficacy and Safety of SI-B001 in Combination With Chemotherapy in the Treatment of EGFR WT and ALK WT Recurrent and Metastatic Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: NSCLC
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-08-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This multi-center, open label phase II clinical study is performed in patients with locally advanced or metastatic EGFR wild-type ALK wild-type non-small cell lung cancer progressed on prior anti-PD-1 mab ± platinum-based chemotherapy. This study is investigating the safety and efficacy of SI-B001 at optimal combination dose with chemotherapy in patients.


Eligibility criteria: Inclusion Criteria:

1. Voluntarily sign informed consent forms and follow program requirements；
2. Male or female;
3. Age: ≥ 18 years;
4. Expected survival time ≥ 3 months;
5. Patients with locally advanced or metastatic EGFR wild-type ALK wild-type lung cancer, disease progression or intolerance after first-line treatment with anti-PD-1/PD-L1 antibody, disease progression or intolerance after first-line treatment with anti-PD-1/PD-L1 antibody and platinum-based chemotherapy, or progression or intolerance after first-line treatment with anti-PD-1/PD-L1 monoclonal antibody;
6. The subject agrees to provide archival tumor tissue samples or fresh tissue samples of the primary tumor or metastases within 6 months; if the subject is unable to provide tumor tissue samples and the subject is unable to provide the gene sequencing report, the subject shall agree to complete the ctDNA EGFR detection during the screening period, and can be assessed by the investigator if other inclusion criteria are met;
7. Must have at least one measurable lesion as defined by RECISTv1.1;
8. Performance status score ECOG0 or 1;
9. Toxicities from prior anticancer therapy have recovered to grade ≤ 2 as defined by NCI-CTCAEv5.0 (except alopecia);
10. No severe cardiac dysfunction, left ventricular score ≥ 50%;
11. The level of organ function must meet the following criteria:

    1. Bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 80 × 109/L, hemoglobin ≥ 90 g/L;
    2. Liver function: TBIL ≤ 1.5ULN (total bilirubin ≤ 3ULN for subjects with Gilbert's syndrome, liver cancer or liver metastases); AST and ALT ≤ 2.5ULN for subjects without liver metastases; AST and ALT ≤ 5.0ULN for subjects with liver metastases;
    3. Renal function: creatinine (Cr) ≤ 1.5ULN, or creatinine clearance (Ccr) ≥ 50 mL/min (according to CockcroftandGault formula).
12. Coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, and activated partial thromboplastin time (APTT) ≤ 1.5ULN;
13. Urine protein ≤ 2 + (measured by dipstick) or \< 1000 mg/24 h (urine);
14. Premenopausal women of childbearing potential must have a negative serum or urine pregnancy test 7 before starting treatment and must be non-lactating; all patients (male or female) should take adequate barrier contraception measures throughout the treatment cycle and 6 months after the end of treatment.

Exclusion Criteria:

1. Patients with past use of docetaxel；
2. Prior to signing the informed consent, the gene sequencing or ctDNA testing report of the previous tissue samples indicated the presence of MET 14 exon jump positive, ROS1 rearrangement positive, BRAF V600E mutation positive, NTRK fusion positive, RET rearrangement positive, HER2 mutation positive, HER2 amplification positive, Patients with KRAS G12C mutation positive；
3. Chemotherapy, biotherapy, immunotherapy, radical radiotherapy, and major surgery were used within 4 weeks before the first administration; palliative radiotherapy, targeted therapy (including small-molecule tyrosine kinase inhibitors) and other antitumor therapy were used within 2 weeks;
4. Screening the history of severe heart disease within the first six months, such as: symptomatic congestive heart failure (CHF) ≥2 (CTCAE v5.0) history, New York Heart Society (NYHA) ≥2 heart failure, acute coronary syndrome, etc.;
5. Prolonged QT interval (QTc \> 450 msec in men or 470 msec in women), complete left bundle branch block, and Degree III atrioventricular block;
6. Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, except for type I diabetes, hypothyroidism controllable by replacement therapy only, skin diseases not requiring systemic treatment (such as vitiligo, psoriasis);
7. Other malignancies diagnosed within 5 years prior to first dose,Exceptions include: radical basal cell carcinoma of the skin, scaly cell carcinoma of the skin, and/or radical resection of carcinoma in situ;
8. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg);
9. Pulmonary disease defined as ≥ grade 3 according to CTCAEv5.0, including resting dyspnea, or requiring continuous oxygen therapy, or patients with a history of interstitial lung disease (ILD);
10. Symptoms of active central nervous system metastases.However, patients with stable parenchymal metastases can be stable, and whether it is stable or not is judged by the investigator;
11. Patients with a history of hypersensitivity to recombinant humanized antibodies or human-mouse chimeric antibodies or hypersensitivity to SI-B001 or any of the excipient components of Osimertinib;
12. History of autologous or allogeneic stem cell transplantation;
13. In previous anthracycline (neo) adjuvant therapy, the cumulative dose of anthracycline was \> 360 mg/m2;
14. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number \> 104) or hepatitis C virus (HCV) infection;
15. Active infection requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;
16. Received other unmarketed clinical study drugs or treatments within 4 weeks prior to study participation;
17. Other conditions for trial participation were not considered by the investigator to be appropriate.

Primary outcomes:
measure: ORR
timeFrame: Up to approximately 24 months
measure: Optimal combination dose (only IIa)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: OS
timeFrame: Up to approximately 24 months
measure: PFS
timeFrame: Up to approximately 24 months
measure: DCR
timeFrame: Up to approximately 24 months
measure: DOR
timeFrame: Up to approximately 24 months
measure: TEAE
timeFrame: Up to approximately 24 months
measure: Cmax
timeFrame: Up to approximately 24 months
measure: Tmax
timeFrame: Up to approximately 24 months
measure: Ctrough
timeFrame: Up to approximately 24 months
measure: ADA
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center (SYSUCC)
state: Guangdong
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guilin
country: China
facility: The Second Affiliated Hospital of Guilin Medical University
state: Guangxi Zhuang Autonomous Region
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Taizhou
country: China
facility: TaiZhou Hospital of Zhejiang Province
state: Zhejiang
Study officials:
affiliation: Sun Yat-sen University Cancer Center (SYSUCC)
name: Li Zhang
role: PRINCIPAL_INVESTIGATOR
References: