NSCLC
Conditions
Brief summary
A randomized, double blind, multicenter phase3 study .
Detailed description
A randomized, double blind, multicenter phase3 study in chemotherapy naive patients with stage IIIB,IV or recurrent NSCLC of non-squamous. the study will randomize about 436 patients at a 1:1 ratio to 2 treatment arms. The study is divided 4 phase, screening, combination treatment, maintenance and follow up.
Interventions
DRUGBevacizumab in Combination With Paclitaxel/Carboplatin
Drug Bevacizumab15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg
DRUGIBI305 in Combination with Paclitaxel/Carboplatin
Drug IBI305 15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg
Sponsors
WuXi CDS Clinical Research (Shanghai) Co.Ltd.
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. signed inform consent form(ICF) 2. Age ≥ 18 years and ≤ 75 years, male or female 3. Histologically or cytologically documented inoperable, local advanced (stage IIIB), metastatic (stage IV), or recurrent non-squamous NSCLC; Mixed tumors should be categorized according to the predominant cell type 4. Histologically confirmed epidermal growth factor receptor (EGFR) wild type or insensitive mutation 5. At least one measurable lesion according to Response Evaluation Criteria In Solid Tumors（RECISIT） v 1.1 6. Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1 7. Life expectancy ≥ 6 months 8. Laboratory results: 1. Adequate hematologic function, defined as absolute neutrophil count ≥1.5×10\^9 /L, platelet count ≥100 ×10\^9 /L, hemoglobin ≥90g/L; 2. Adequate liver function, defined as total bilirubin levels ≤ 1.5 times normal upper limit (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN, or AST and ALT levels ≤ 5 times ULN for patients with hepatic metastasis; 3. Adequate renal function, defined as serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 50 ml / min (Cockcroft-Gault formula) and proteinuria \< 2+; 4. Coagulation function is adequate, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times normal upper limit (ULN), PTT or aPTT ≤ 1.5 times ULN; 9. Expected protocol compliance 10. Patients of childbearing potential must agree to use effective contraceptive measures during study treatment and for 6 months after receiving last study treatment (e.g. abstinence, sterilization surgery, oral contraceptives, contraception by progesterone injection or subcutaneous).
Exclusion criteria
1. Prior chemotherapy or target therapy with another systemic anti-cancer agent (e.g., monoclonal antibody, tyrosine kinase inhibitor) for the treatment of the patient's current stage of disease (Stage IIIB not amenable for combined modality treatment, stage IV or recurrent disease). Prior surgery and irradiation is permitted, provided that the criteria outlined in the protocol for both treatments are met. Disease progressed within 6 months after adjuvant therapy must be excluded. 2. Mixed non-small cell and small cell carcinoma, or mixed adenosquamous carcinomas with predominant squamous cell 3. Histologically or cytologically confirmed EGFR sensitive mutation type, unknown EGFR status for any reason is allowed in this study. 4. Known hemoptysis within 3 months prior to screening with blood volume more than 2.5 mL each time 5. Evidence of tumor invading major blood vessels on imaging. The investigator or the local radiologist must exclude evidence of tumor that is fully contiguous with, surrounding, or extending into the lumen of a major blood vessel (e.g., pulmonary artery or superior vena cava) 6. Evidence of brain metastasis, spinal cord compression or carcinomatous meningitis history with clinical symptoms. For stable patients with no symptom, could be admitted if fulfill all below criteria: measurable lesion(s) out of CNS, no metastasis at mesocephalon, annular protuberance, medulla oblongata and spinal cord; no history of intracranial bleeding. 7. Radical radiotherapy to the thorax with curative intent within 28 days prior to enrollment; palliative radiotherapy for bone lesions outside the thoracic region within 2 weeks prior to first dose of study treatment. 8. Serious, non-healing wound, active ulcer, or untreated bone fracture, or major surgical procedure within 28 days prior to randomization or anticipation of need for major surgery during the course of the study. 9. Minor surgery (Including insertion of an indwelling catheter) within 48 hours prior to first dose of study treatment 10. Recent or current (within 10 days prior to first dose of study treatment) receive treatment of Aspirin (\> 325 mg/day) or other non-steroidal anti-inflammatory drugs (NSAID) known to inhibit platelet function (within 10 days prior to first dose of study treatment) 11. Recent or current receive treatment of oral all doses of oral or parenteral anticoagulants or thrombolytic agent. Prophylactic use of anticoagulants is permitted. 12. History or evidence of inherited bleeding diathesis or coagulopathy or thrombus 13. Uncontrolled hypertension (SBP\>140 mmHg and/or diastolic blood pressure\>90 mmHg), prior history of hypertensive crisis and hypertensive encephalopathy 14. Clinically significant cardiovascular disease but not limited to active infections; unstable angina; stroke or transient cerebral ischemia (within 6 months prior to screening); myocardial infarction (within 6 months prior to screening) ; congestive heart-failure (New York Heart Association (NYHA) class≥ II) ; serious cardiac arrhythmia, hepatic, renal or metabolic disease requiring medication during the study. 15. History of peptic ulcer, gastrointestinal perforation, erosive esophagitis, erosive gastritis, inflammatory bowel disease or diverticulitis, abdominal fistula or intra-abdominal abscess within 6 months prior to screening 16. Patient diagnosed with a tracheo-esophageal fistula 17. Clinically significant third space effusion (e.g., uncontrolled ascites or pleural effusion by extraction or other treatment) 18. Pulmonary fibrosis or active pneumonia showed by CT at baseline 19. Active malignancy other than non-small cell lung cancer (NSCLC), treated carcinoma in situ of the cervix, superficial basal cell or squamous cell carcinoma, radical surgery of localized prostate cancer, radical surgery of ductal carcinoma in situ within 5 years prior to randomization 20. Known autoimmune disease 21. Known positive HbsAg and hepatitis B virus (HBV)-DNA drop test in peripheral blood ≥ 1 x 10\^3 copy number/L or 200 IU/mL; If HBsAg positive and HBV-DNA drop test in peripheral blood \< 1 x 10\^3 copy number/L or 200 IU/mL, patient is considered to be eligible by investigator only when chronic hepatitis B in the plateau and do not increase the risk 22. Known positive HIV or hepatitis C virus (HCV) or syphilis 23. Known allergic disease or allergic physique 24. Treatment with any other investigational agent or participation in another clinical trial within 30 days prior to screening 25. Known alcoholism or drug abuse 26. Pregnant or anticipation of pregnant during the study or lactating women 27. Known hypersensitivity to bevacizumab or any of its excipients and/or any of the chemotherapy agents 28. Other conditions that the investigator thinks unsuitable in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 18 weeks | ORR（objective response rate）was defined as the percentage of participants in the analysis population who had a Complete Response or a Partial Response per RECIST 1.1. The percentage of participants who experienced a CR or PR is presented. Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Time | 18.020 months | OS was defined as the time from randomization to death due to any cause. |
| Progression-free Survival | 18 months | Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Independent Radiological Review Committee.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab in Combination With Paclitaxel/Carboplatin Drug Bevacizumab15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg | 220 |
| IBI305 in Combination With Paclitaxel/Carboplatin Drug IBI305 15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg | 221 |
| Total | 441 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | allergic reaction | 2 | 1 |
| Overall Study | non-measurable lesions at baseline | 1 | 2 |
| Overall Study | Protocol Violation | 3 | 0 |
Baseline characteristics
| Characteristic | Bevacizumab in Combination With Paclitaxel/Carboplatin | IBI305 in Combination With Paclitaxel/Carboplatin | Total |
|---|---|---|---|
| Age, Continuous Mean (SD) | 57.6 years STANDARD_DEVIATION 8.69 | 57.2 years STANDARD_DEVIATION 9.28 | 57.4 years STANDARD_DEVIATION 8.98 |
| Height | 164.93 centimeter STANDARD_DEVIATION 8.166 | 164.03 centimeter STANDARD_DEVIATION 7.829 | 164.48 centimeter STANDARD_DEVIATION 8.003 |
| Race/Ethnicity, Customized Han | 217 Participants | 211 Participants | 428 Participants |
| Race/Ethnicity, Customized Others | 4 Participants | 9 Participants | 13 Participants |
| Region of Enrollment China | 220 participants | 221 participants | 441 participants |
| Sex: Female, Male Female | 83 Participants | 79 Participants | 162 Participants |
| Sex: Female, Male Male | 137 Participants | 142 Participants | 279 Participants |
| Weight | 62.16 kilogram STANDARD_DEVIATION 10.844 | 62.14 kilogram STANDARD_DEVIATION 10.272 | 62.15 kilogram STANDARD_DEVIATION 10.55 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 226 | 6 / 224 |
| other Total, other adverse events | 222 / 226 | 216 / 224 |
| serious Total, serious adverse events | 85 / 226 | 75 / 224 |
Outcome results
Primary
Objective Response Rate
ORR（objective response rate）was defined as the percentage of participants in the analysis population who had a Complete Response or a Partial Response per RECIST 1.1. The percentage of participants who experienced a CR or PR is presented. Overall Response (OR) = CR + PR.
Time frame: 18 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab in Combination With Paclitaxel/Carboplatin | Objective Response Rate | 46.4 percentage of participants |
| IBI305 in Combination With Paclitaxel/Carboplatin | Objective Response Rate | 44.3 percentage of participants |
90% CI: [0.756, 1.077]
Secondary
Overall Survival Time
OS was defined as the time from randomization to death due to any cause.
Time frame: 18.020 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab in Combination With Paclitaxel/Carboplatin | Overall Survival Time | NA month |
| IBI305 in Combination With Paclitaxel/Carboplatin | Overall Survival Time | 18.020 month |
p-value: 0.7066Log Rank
Secondary
Progression-free Survival
Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Independent Radiological Review Committee.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab in Combination With Paclitaxel/Carboplatin | Progression-free Survival | 8.260 months |
| IBI305 in Combination With Paclitaxel/Carboplatin | Progression-free Survival | 8.430 months |
p-value: 0.3497Log Rank