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

Phase 2

Completed

• Conditions: Small-cell Lung Cancer
• Interventions: Drug: SHR-1210; Drug: Apatinib

• Registration Number: NCT03417895
• Lead Sponsor: 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 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-01-08
• Study First Submitted QC: 2018-01-29
• Study First Posted: 2018-01-31
• Study Start: 2018-04-20
• Primary Completion: 2021-08-04
• Study Completion: 2021-08-04
• Status Verified: 2023-04
• Results First Submitted: 2023-04-12
• Results First Submitted QC: 2024-02-25
• Last Update Submitted: 2024-02-25
• Results First Posted: 2024-08-07
• Last Update Posted: 2024-08-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A (SHR-1210+Apatinib)	SHR-1210	SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD
B (SHR-1210+Apatinib)	SHR-1210	SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (5 Days on, 2 Days off)
A (SHR-1210+Apatinib)	Apatinib	SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD
B (SHR-1210+Apatinib)	Apatinib	SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (5 Days on, 2 Days off)
C (SHR-1210+Apatinib)	SHR-1210	SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (7 Days on, 7 Days off)
C (SHR-1210+Apatinib)	Apatinib	SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (7 Days on, 7 Days off)

Primary Outcome Measures

Name	Time	Method
Adverse Event	24 months	Evaluation of adverse event rate according to CTCAE v4.03
ORR	6 months	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)

Secondary Outcome Measures

Name	Time	Method
PFS	Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.	Progression-free survival according to RECIST v1.1
DCR	Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.	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
OS Rate	6 months	Overall survival rate
TTR	Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.	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)
DoR	Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.	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
OS	on average of 2 years	Overall survival

Trial Locations

Locations (2)

Cancer Hospital Chinese Academy of Medical Science; 🇨🇳 Beijing, Beijing, China

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China