SI-B001 Combined With Osimertinib Mesylate Tablets in the Treatment of Recurrent Metastatic Non-small Cell Lung Cancer.
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2/Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SI-B001 combined with osimertinib_A Patients with locally advanced/metastatic NSCLC progressed on 3rd generation EGFR-TKI treatment. |
Drug: SI-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).
Drug: Osimertinib
Osimertinib is administered at the recommended dose of 80mg daily.
|
| Experimental: SI-B001 combined with osimertinib_B Patients with locally advanced/metastatic NSCLC progressed on prior EGFR-TKI treatment and with T790M negative mutation. |
Drug: SI-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).
Drug: Osimertinib
Osimertinib is administered at the recommended dose of 80mg daily.
|
| Experimental: SI-B001 combined with osimertinib_C Patients with locally advanced/metastatic NSCLC and with EGFR exon20ins mutation. |
Drug: SI-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).
Drug: Osimertinib
Osimertinib is administered at the recommended dose of 80mg daily.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female;
-
Age: ≥ 18 years;
-
Expected survival time ≥ 3 months;
-
Histopathologically and/or cytologically confirmed locally advanced or metastatic
NSCLC patients who are enrolled in 3 cohorts:
- patients progressed on prior 1st line or 2nd line 3rd generation EGFR-TKI treatment; B) patients progressed on prior 1st line 1st or 2nd generation EGFR-TKI treatment and with T790M negative mutation; C) patients with EGFR exon20ins mutation;
-
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;
-
Must have at least one measurable lesion as defined by RECISTv1.1;
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Performance status score ECOG0 or 1;
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Toxicities from prior anticancer therapy have recovered to grade ≤ 2 as defined by NCI-CTCAEv5.0 (except alopecia);
-
No severe cardiac dysfunction, left ventricular score ≥ 50%;
-
The level of organ function must meet the following criteria:
-
Bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 80 × 109/L, hemoglobin ≥ 90 g/L;
-
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;
-
Renal function: creatinine (Cr) ≤ 1.5ULN, or creatinine clearance (Ccr) ≥ 50 mL/min (according to CockcroftandGault formula).
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Coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, and activated partial thromboplastin time (APTT) ≤ 1.5ULN;
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Urine protein ≤ 2 + (measured by dipstick) or < 1000 mg/24 h (urine);
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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:
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Patients with MET, ALK, RET, HER2 mutations suggested by gene sequencing;
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Patients who have previously received systemic chemotherapy in the first/second line of systemic therapy;
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Use chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery before the first dose;
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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;
-
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);
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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;
-
Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure
150 mmHg or diastolic blood pressure > 100 mmHg);
-
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);
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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;
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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;
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History of autologous or allogeneic stem cell transplantation;
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In previous anthracycline (neo) adjuvant therapy, the cumulative dose of anthracycline was > 360 mg/m2;
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Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > 104) or hepatitis C virus (HCV) infection;
-
Active infection requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;
-
Received other unmarketed clinical study drugs or treatments before participating in the study;
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sun Yat-sen University Cancer Center (SYSUCC) | Guangdong | Guangzhou | China |
Sponsors and Collaborators
- Sichuan Baili Pharmaceutical Co., Ltd.
Investigators
- Principal Investigator: Li Zhang, Sun Yat-sen University Cancer Center (SYSUCC)
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SI-B001_210