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A Study of SHR-1210 in Combination With Apatinib in Advanced Non-Small Cell Lung Cancer(NSCLC)

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ClinicalTrials.gov Identifier: NCT03083041
Recruitment Status : Recruiting
First Posted : March 17, 2017
Last Update Posted : February 7, 2018
Sponsor:
Information provided by (Responsible Party):
Jiangsu HengRui Medicine Co., Ltd.

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.


Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Biological: SHR-1210 Drug: Apatinib Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 118 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of SHR-1210 in Combination With Apatinib in Advanced Non-Small Cell Lung
Actual Study Start Date : March 22, 2017
Estimated Primary Completion Date : December 27, 2018
Estimated Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: SHR-1210,200mg,q2w plus apatinib 250mg/d
SHR-1210 200mg, IV, Q2W and Apatinib 250mg, PO, QD
Biological: SHR-1210
SHR-1210 will be administered as a 30-minute IV infusion Q2W at a dose of 200mg
Drug: Apatinib
Apatinib tablet will be administered orally,once daily until progression
Other Name: Apatinib Mesylate
Experimental: SHR-1210,200mg,q2w plus apatinib 500mg/d
SHR-1210 200mg, IV, Q2W and Apatinib 500mg, PO, QD
Biological: SHR-1210
SHR-1210 will be administered as a 30-minute IV infusion Q2W at a dose of 200mg
Drug: Apatinib
Apatinib tablet will be administered orally,once daily until progression
Other Name: Apatinib Mesylate
Experimental: SHR-1210,200mg,q2w plus apatinib 375mg/d
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD
Biological: SHR-1210
SHR-1210 will be administered as a 30-minute IV infusion Q2W at a dose of 200mg
Drug: Apatinib
Apatinib tablet will be administered orally,once daily until progression
Other Name: Apatinib Mesylate



Primary Outcome Measures :
  1. Part 1: Incidence and grade of adverse events (AEs) and Serious adverse events (SAEs) [ Time Frame: up to 24 weeks ]
    AEs and SAEs assessed by NCI-CTCAE v4.03

  2. Part 2:Objective response rate (ORR) per RECIST 1.1 [ Time Frame: Up to approximately 6 months ]
    ORR is defined as the proportion of subjects who have achieved complete response (CR) or partial response (PR) according to RECIST 1.1


Secondary Outcome Measures :
  1. Part 1: Apatinib plasma concentrations and serum SHR-1210 concentrations [ Time Frame: Cycles 1-2(each cycle is 28 days) ]
    Apatinib plasma concentrations and serum SHR-1210 concentrations in Expansion cohort

  2. Part 1:Peak Plasma Concentration (Cmax) of Apatinib and SHR-1210 [ Time Frame: Cycles 1-2(each cycle is 28 days) ]
    Cmax of Apatinib and SHR-1210 in Expansion cohort

  3. Part 1:Objective response rate (ORR) - RECIST 1.1 [ Time Frame: Up to approximately 6 months ]
    ORR is defined as the proportion of subjects who have achieved complete response (CR) or partial response (PR) according to RECIST 1.1

  4. Duration of Response (DoR) [ Time Frame: Up to approximately 2 years ]
    Duration of Response (DoR) per RECIST 1.1

  5. Progression-free survival(PFS) [ Time Frame: Up to approximately 2 years ]
    PFS per RECIST 1.1

  6. Overall survival rate at 12 months (OSR12) [ Time Frame: Up to approximately 1 years ]
    OSR12 will be calculated based on Kaplan-Meier estimates of Overall survival at 12 months

  7. Part 1: Area under the plasma concentration-time curve from time 0 to 24 hrs, AUC[0-24] [ Time Frame: Cycles 1-2(each cycle is 28 days) ]
    AUC[0-24] of Apatinib and SHR-1210 in Expansion cohort



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03083041


Contacts
Contact: Xiaoyan Kang, MD 021-60453139 kangxiaoyan@shhrp.com
Contact: Shu Wang +86 18036618586 wangshu@hrs.com.cn

Locations
China, Shanghai
Shanghai Pulmonary Hospital Recruiting
Shanghai, Shanghai, China, 200433
Contact: caicun zhou    86-021-65115006      
Sponsors and Collaborators
Jiangsu HengRui Medicine Co., Ltd.

Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier: NCT03083041     History of Changes
Other Study ID Numbers: SHR-1210-APTN-II-202-NSCLC
First Posted: March 17, 2017    Key Record Dates
Last Update Posted: February 7, 2018
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jiangsu HengRui Medicine Co., Ltd.:
SHR-1210
Apatinib
NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases