A Phase II/III Clinical Study to Evaluate the Efficacy and Safety of SI-B001 in Combination With Osimertinib Mesylate Tablets in the Treatment of Recurrent and Metastatic Non- Small Cell Lung Cancer

• 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 Osimertinib 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 Osimertinib.

• 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. Histopathologically and/or cytologically confirmed T790M-negative locally advanced or metastatic lung cancer patients who are resistant after the first/second line of third-generation EGFRTKI or resistant after the first/second line of TKI;

5. Agree to provide archival tumor tissue samples or fresh tissue samples of the primary tumor or metastases within 6 months; if the subject cannot provide tumor tissue samples, they can be evaluated by the investigator if they meet other inclusion and exclusion criteria;

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. Patients with MET, ALK, RET, HER2 mutations suggested by gene sequencing;

2. Patients who have previously received systemic chemotherapy in the first/second line of systemic therapy;

3. Use chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery before the first dose;

4. 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;

5. 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);

6. 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;

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

8. 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);

9. 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;

10. 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;

11. History of autologous or allogeneic stem cell transplantation;

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

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

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

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