A Phase II/III Study of SI-B001 in Combination With Osimertinib in the Treatment of EGFR/ALK WT Recurrent and Metastatic NSCLC

• Status: Not yet recruiting
• Trial end date: 2023-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Main purpose:

1. To explore the efficacy of SI-B001 at RP2D obtained in phase I clinical trial and single low dose combined with chemotherapy in patients with locally advanced or metastatic NSCLC.

2. To explore the safety and tolerability of SI-B001 in patients with locally advanced or metastatic lung cancer (NSCLC) at RP2D obtained in phase I clinical trial and single-dose low-dose combination chemotherapy, and to select the optimal dose (combined with RP2D) and mode of SI-B001 combined with chemotherapy.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.

Criteria

Inclusion Criteria:

1. Male or female;

2. Age: ≥ 18 years;

3. Expected survival time ≥ 3 months;

4. 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;

5. 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 ctDNAEGFR detection during the screening period, and can be assessed by the investigator if other inclusion criteria are met;

6. Must have at least one measurable lesion as defined by RECISTv1.1;

7. Performance status score ECOG0 or 1;

8. Toxicities from prior anticancer therapy have recovered to grade ≤ 2 as defined by NCI-CTCAEv5.0 (except alopecia);

9. No severe cardiac dysfunction, left ventricular score ≥ 50%;

10. 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).

11. Coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, and activated partial thromboplastin time (APTT) ≤ 1.5ULN;

12. Urine protein ≤ 2 + (measured by dipstick) or < 1000 mg/24 h (urine);

13. 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. Use of chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery before the first dose; 2. Use of palliative radiotherapy, targeted therapy (including small molecule tyrosine kinase inhibitors) and other anti-tumor therapy;

2. History of significant cardiac disease, such as: symptomatic congestive heart failure (CHF) ≥ grade 2 (CTCAE 5.0) history, New York Heart Association (NYHA) ≥ grade 2 heart failure, acute coronary syndrome, etc.; QT prolongation (QTc > 450 msec in men or QTc > 470 msec in women), complete left bundle branch block, third degree atrioventricular block;

3. 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);

4. 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;

5. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg);

6. 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);

7. 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;

8. 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;

9. History of autologous or allogeneic stem cell transplantation;

10. In previous anthracycline (neo) adjuvant therapy, the cumulative dose of anthracycline was > 360 mg/m2;

11. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > 104) or hepatitis C virus (HCV) infection;

12. Active infection requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;

13. Received other unmarketed clinical study drugs or treatments before participating in the study;