Combining SI-B001 with chemotherapy for treating advanced lung cancer

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

This study is testing if adding a new treatment called SI-B001 to chemotherapy can help people with advanced lung cancer who haven't responded well to previous therapies.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: Osimertinib, chemotherapy, immunotherapy
• Locations: 6 sites (Chongqing, Chongqing and 5 other locations)
• Trial ID: NCT05020457 on ClinicalTrials.gov

What this trial studies

This multi-center, open-label phase II clinical study investigates the safety and efficacy of SI-B001 in combination with chemotherapy for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is EGFR and ALK wild-type. Participants must have experienced disease progression or intolerance after prior treatments with anti-PD-1 antibodies and platinum-based chemotherapy. The study aims to determine the optimal combination dose of SI-B001 with chemotherapy to improve patient outcomes. Archival or fresh tumor tissue samples will be collected for analysis.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with EGFR wild-type and ALK wild-type NSCLC who have progressed after prior anti-PD-1 therapy and platinum-based chemotherapy.

Not a fit: Patients with non-recurrent or early-stage lung cancer, or those who have not received prior anti-PD-1 therapy, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced NSCLC who have limited treatment alternatives.

How similar studies have performed: Other studies have explored similar combinations of targeted therapies and chemotherapy in NSCLC, showing promising results, but this specific combination is novel.

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.

Where this trial is running

Chongqing, Chongqing and 5 other locations

• Chongqing University Cancer Hospital — Chongqing, Chongqing, China (Recruiting)
• Sun Yat-sen University Cancer Center (SYSUCC) — Guangzhou, Guangdong, China (Recruiting)
• The Second Affiliated Hospital of Guangzhou Medical University — Guangzhou, Guangdong, China (Recruiting)
• The Second Affiliated Hospital of Guilin Medical University — Guilin, Guangxi Zhuang Autonomous Region, China (Recruiting)
• Shandong Cancer Hospital — Jinan, Shandong, China (Recruiting)
• TaiZhou Hospital of Zhejiang Province — Taizhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Li Zhang — Sun Yat-sen University Cancer Center (SYSUCC)
• Study coordinator: Sa Xiao, PHD

Conditions Non Small Cell Lung Cancer; NSCLC