Non-small Cell Lung Cancer
Conditions
Keywords
NSCLC
Brief summary
This multi-center, open label Phase II/III clinical study is performed in patients with locally advanced/metastatic NSCLC progressed on prior EGFR-TKI treatment or with non TKI-sensitizing mutation or patients with EGFR exon20ins mutation. This study is investigating the safety and efficacy of SI-B001 at monotherapy RP2D or lower combined with Osimertinib in patients with locally advanced or metastatic NSCLC.
Interventions
DRUGSI-B001
SI-B001 is administered by intravenous drip once weekly (QW). 120 min ± 10 min after the first intravenous drip, if the infusion reaction is tolerable during the first dose, the subsequent infusion can be completed within 60-120 min (unless agreed or required by the investigator, the infusion time can be extended).
DRUGOsimertinib
Osimertinib is administered at the recommended dose of 80mg daily.
Sponsors
Sichuan Baili Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntarily sign the informed consent and follow the requirements of the protocol; 2. Male or female; 3. Age: ≥ 18 years; 4. Expected survival time ≥ 3 months; 5. Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) confirmed by histopathology and/or cytology, T790M-negative, Exon20ins mutation resistant to the third generation EGFR TKI after the first or second line treatment, or resistance to the first or second generation TKI after the first line treatment; 6. Consent to provide an archived tumor tissue specimen or fresh tissue sample (an FFPE block or approximately 6-12 white slides with a size of 5μm) from the primary or metastatic tumor within 6 months of the date of consent. Participants who were unable to provide tumor tissue samples could be enrolled if they met other inclusion and
Exclusion criteria
after evaluation by investigators. 7. Must have at least one measurable lesion as defined by RECISTv1.1; 8. Performance status score ECOG0 or 1; 9. Toxicity from previous antineochemical therapy has returned to grade 1 or less as defined by NCI-CTCAE v5.0 (asymptomatic laboratory abnormalities such as elevated ALP, hyperuricemia, elevated serum amylase/lipase, and elevated blood glucose were considered by the investigator, and toxicity with no safety risk was judged by the investigator; Except for alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stable with hormone replacement therapy). 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 × 10\^9/L, platelet count ≥ 80 × 10\^9/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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | Up to approximately 24 months | Objective Response Rate |
| Optimal combination dose (only Phase IIa) | Up to approximately 24 months | Optimal combination dose for SI-B001 and Osimertinib (only IIa) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
China
Outcome results
None listed