SHR-1210 Combined With Apatinib in Treatment of ED-SCLC After Failure of First Line Standard Therapy

Jiangsu HengRui Medicine Co., Ltd.59 enrolled

Overview

This is a multi-center, open-label, phase II study of intravenous (IV) SHR-1210 at 200mg,q2w in combination with Apatinib at one dose (375mg). Comparison of 3 different dose schedules in subjects with extensive-stage disease small cell lung cancer. 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). The study is composed of two parts. Part 1 of the study will determine the safety and tolerability of SHR-1210 in combination with Apatinib in first 6 subjects of each arm. The second phase of treatment was carried out by selecting one group of administration mode and the tolerated dose of Apatinib. Part 2 of the study will determine the safety and efficacy of SHR-1210 in combination with Apatinib in 39 subjects.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Small-cell Lung Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Signed inform consent form. 2. Age \>= 18 years and \<= 70 years. 3. Histologically or cytologically confirmed small cell lung cancer. 4. ED-SCLC according to Veterans Administration Lung Study Group. 5. Radiographically progression following a platinum-based standard prior chemotherapy regimen. 6. Eastern Cooperative Oncology Group performance status of 0 or 1. 7. Measurable disease as defined by RECIST v1.1. 8. Life expectancy \>= 8 weeks. 9. Adequate hematologic and end organ function. Exclusion Criteria: 1. Histologically or cytologically confirmed mixed non-small cell and small cell carcinoma. 2. Prior exposure to therapeutic anticancer vaccines; prior exposure to any T cell co-stimulatory therapy or immune checkpoint inhibitors, including but not limited to other anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-PD-L2 antibodies. 3. Prior exposure to anti-VEGF or anti-VEGFR therapy. 4. Active brain metastasis or meningeal metastasis. 5. Clinically significant third space effusion (e.g., uncontrolled pericardial effusion, ascites or pleural effusion by extraction or other treatment). 6. Known hypersensitivity to study drug or any of its excipients; known hypersensitivity to any antibody. 7. Treatment with any other investigational agent or participation in another clinical trial within 4 weeks prior to screening. 8. Other conditions that the investigator thinks unsuitable in this study.

Locations (2)

Cancer Hospital Chinese Academy of Medical Science

Beijing, Beijing Municipality, China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Outcomes

Primary Outcomes

Adverse Event

Evaluation of adverse event rate according to CTCAE v4.03

Time frame: 24 months

ORR

Objective response rate according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Over all response：CR+PR)

Time frame: 6 months

Secondary Outcomes

OS Rate

Overall survival rate

Time frame: 6 months

PFS

Progression-free survival according to RECIST v1.1

Time frame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.

TTR

Time to response according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Time to response (TTR): date of first dose to date of first documented CR or PR)

Time frame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.

DoR

Duration of response according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Duration of response (DoR): DoR will only be performed in subjects who have a confirmed tumor response (CR or PR) after treatment

Time frame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.

DCR

Disease control rate according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1; Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Disease control rate (DCR): CR+PR+SD

Time frame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.

Overall survival

Time frame: on average of 2 years