SI-B001 Combined With Chemotherapy in the Treatment of EGFR/ALK WT Recurrent or Metastatic NSCLC.

Phase 2

Recruiting

• Conditions: Non Small Cell Lung Cancer
• Interventions: Drug: SI-B001; Drug: AP or TP; Drug: Docetaxel

• Registration Number: NCT05020457
• Lead Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-08-22
• Study First Submitted QC: 2021-08-22
• Study First Posted: 2021-08-25
• Study Start: 2021-12-07
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-12
• Last Update Posted: 2024-10-15
• Primary Completion: 2025-06
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
SI-B001 combined with AP or TP_A	AP or TP	SI-B001 combined with Platinum-based chemotherapy(AP or TP). Patients enrolled with EGFRwt/ALKwt NSCLC progressed or were intolerant after first-line treatment with anti-PD-1 /L1 mab alone.
SI-B001 combined with Docetaxel_B	SI-B001	Patients with EGFRwt/ALKwt non-small cell lung cancer were included and progressed or were intolerant after first-line treatment with platinum-based two-drug chemotherapy plus anti-PD-1 /L1 mab.
SI-B001 combined with AP or TP_A	SI-B001	SI-B001 combined with Platinum-based chemotherapy(AP or TP). Patients enrolled with EGFRwt/ALKwt NSCLC progressed or were intolerant after first-line treatment with anti-PD-1 /L1 mab alone.
SI-B001 combined with Docetaxel_C	SI-B001	Patients enrolled with EGFRwt/ALKwt NSCLC progressed or were intolerant to treatment with anti-PD-1 /PD-L1 monoclonal antibody after first-line or above chemotherapy.
SI-B001 combined with Docetaxel_C	Docetaxel	Patients enrolled with EGFRwt/ALKwt NSCLC progressed or were intolerant to treatment with anti-PD-1 /PD-L1 monoclonal antibody after first-line or above chemotherapy.
SI-B001 combined with Docetaxel_B	Docetaxel	Patients with EGFRwt/ALKwt non-small cell lung cancer were included and progressed or were intolerant after first-line treatment with platinum-based two-drug chemotherapy plus anti-PD-1 /L1 mab.

Primary Outcome Measures

Name	Time	Method
ORR	Up to approximately 24 months	Objective Response Rate
Optimal combination dose (only IIa)	Up to approximately 24 months	Optimal combination dose of SI-B001 with chemotherapy (only IIa)

Secondary Outcome Measures

Name	Time	Method
OS	Up to approximately 24 months	Overall Survival
PFS	Up to approximately 24 months	Progression Free Survival
DCR	Up to approximately 24 months	Disease Control Rate
DOR	Up to approximately 24 months	Duration of Response
TEAE	Up to approximately 24 months	Treatment Emergent Adverse Events
Cmax	Up to approximately 24 months	Maximum serum concentration
Tmax	Up to approximately 24 months	Time to maximum serum concentration
Ctrough	Up to approximately 24 months	Minimum serum concentration
ADA	Up to approximately 24 months	anti-SI-B001 antibody

Trial Locations

Locations (6)

Chongqing University Cancer Hospital; 🇨🇳 Chongqing, Chongqing, China

Sun Yat-sen University Cancer Center (SYSUCC); 🇨🇳 Guangzhou, Guangdong, China

The Second Affiliated Hospital of Guilin Medical University; 🇨🇳 Guilin, Guangxi Zhuang Autonomous Region, China

Shandong Cancer Hospital; 🇨🇳 Jinan, Shandong, China

TaiZhou Hospital of Zhejiang Province; 🇨🇳 Taizhou, Zhejiang, China

The Second Affiliated Hospital of Guangzhou Medical University; 🇨🇳 Guangzhou, Guangdong, China