Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
SHR-1210, Apatinib, NSCLC
Brief summary
This is a multi-center, open-label, Phase II study of intravenous (IV) SHR-1210 at 200mg, q2w in combination with Apatinib at two dose levels in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC). The study is composed of two parts. Part 1 of the study will determine the safety, tolerability and pharmacokinetics of SHR-1210 in combination with Apatinib. Part 2 includes a randomized comparison of Apatinib 250mg/d or 500mg/d plus SHR-1210. Subject's tumors will be screened at baseline for EGFR mutations, EML4-ALK translocation, and PD-L1 expression.But positive tumor PD-L1 expression will not be required for enrollment.
Detailed description
SHR-1210 is a humanized monoclonal antibody against Programmed death 1(PD-1). Apatinib is a new kind of selective Vascular Endothelial Growth Factor Receptor 2(VEGFR-2) tyrosine kinase inhibitor (TKI). A disease-control rate of 61.1% and a mPFS of 4.7 months were showed in Apatinib phase II study in patients with NSCLC.
Interventions
BIOLOGICALSHR-1210
SHR-1210 will be administered as a 30-minute IV infusion Q2W at a dose of 200mg
DRUGApatinib
Apatinib tablet will be administered orally,once daily until progression
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects \>/= 18 years and \</=70 years of age at the time of Informed Consent. 2. Advanced relapsed or refractory predominantly NSCLC with at least one measurable lesion according to RECIST 1.1. 3. Failure of second line of chemotherapy(Part 1); Failure of First line of chemotherapy(Part 2) 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 5. Patients must have recovered from any AEs of prior treatments before randomization. 6. Adequate bone marrow,liver and renal function as assessed by the following laboratory tests conducted within 1 week before randomization. HB ≥ 90g/L; ANC≥1.5×10E+9/L; PLT≥100×10E+9/L; ALT and AST \< 1.5×ULN; TBIL ≤1×ULN; Cr ≤1.5×ULN or CL≥60 ml/min. 7. Life expectancy of at least three months. 8. Male or female participants of childbearing potential must be willing to use an adequate method of contraception starting with the first dose of study drug through 60 days for female subjects and 120 days for male subjects after the last dose of study drug. 9. Written informed consent and the willingness and ability to comply with all aspects of the protocol.
Exclusion criteria
1. Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female≥ 470 ms). 2. Severe or uncontrolled systemic disease such as clinically significant hypertension (systolic pressure \>/= 140 mm Hg and/or diastolic pressure \>/= 90 mm Hg), and Grade III-IV cardiac insufficiency, according to NYHA criteria or echocardiography check: LVEF\<50%. 3. Factors to affect oral administration (inability to swallow tablets,GI tract resection, chronic bacillary diarrhea and intestinal obstruction). 4. Coagulation disfunction,hemorrhagic tendency or receiving anticoagulant therapy 5. \>/= CTCAE 2 pneumorrhagia or \>/= CTCAE 3 hemorrhage in other organs within 4 weeks. 6. Bone fracture or wounds that was not cured. 7. Arterial thrombus or phlebothrombosis within 6 months and taking anticoagulant agents. 8. Mental diseases and psychotropic substances abuse. 9. Previous treatment with an trial agent within 4 weeks 10. Proteinuria ≥ (++) or 24 hours total urine protein \> 1.0 g. 11. Other coexisting malignant disease (except basal-cell carcinoma and carcinoma in situ of uterine cervix).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) | from signing the informed consent form to safety follow-up, 61 months | Number of participants with Adverse Events and Serious Adverse Events |
| Objective Response Rate (ORR)： | from first administration to progressive disease or initiation of new anti-cancer therapy, 61 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Countries
China
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 55.0 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 210 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment China | 130 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 48 / 198 | 3 / 12 |
| other Total, other adverse events | 197 / 198 | 12 / 12 |
| serious Total, serious adverse events | 112 / 198 | 7 / 12 |
Outcome results
None listed