Clinical trial NCT03083041: A Study of SHR-1210 in Combination With Apatinib in Advanced Non-Small Cell Lung Cancer(NSCLC)
Official title: A Phase II Study of SHR-1210 in Combination With Apatinib in Advanced Non-Small Cell Lung
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: SHR-1210
Apatinib
NSCLC
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2017-03-17
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Part 1: Incidence and grade of adverse events (AEs) and Serious adverse events (SAEs)
timeFrame: up to 24 weeks
measure: Part 2:Objective response rate (ORR) per RECIST 1.1
timeFrame: Up to approximately 6 months
Secondary outcomes:
measure: Part 1: Apatinib plasma concentrations and serum SHR-1210 concentrations
timeFrame: Cycles 1-2(each cycle is 28 days)
measure: Part 1:Peak Plasma Concentration (Cmax) of Apatinib and SHR-1210
timeFrame: Cycles 1-2(each cycle is 28 days)
measure: Part 1:Objective response rate (ORR) - RECIST 1.1
timeFrame: Up to approximately 6 months
measure: Duration of Response (DoR)
timeFrame: Up to approximately 2 years
measure: Progression-free survival(PFS)
timeFrame: Up to approximately 2 years
measure: Overall survival rate at 12 months (OSR12)
timeFrame: Up to approximately 1 years
measure: Part 1: Area under the plasma concentration-time curve from time 0 to 24 hrs, AUC[0-24]
timeFrame: Cycles 1-2(each cycle is 28 days)
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
Study officials:
References:
citation: Gao G, Ni J, Wang Y, Ren S, Liu Z, Chen G, Gu K, Zang A, Zhao J, Guo R, He J, Lin X, Pan Y, Ma Z, Wang Z, Fan M, Liu Y, Cang S, Yang X, Li W, Wang Q, Zhou C. Efficacy and safety of camrelizumab plus apatinib in previously treated patients with advanced non-small cell lung cancer harboring EGFR or ALK genetic aberration. Transl Lung Cancer Res. 2022 Jun;11(6):964-974. doi: 10.21037/tlcr-22-22.