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

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

A Phase II Study of SHR-1210 in Combination With Apatinib in Advanced Non-Small Cell Lung

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03083041
• Other study ID #: SHR-1210-APTN-II-202-NSCLC
• Status: Completed
• Phase: Phase 2
• Start date: March 22, 2017
• Est. completion date: May 20, 2022

Study information

• Verified date: June 2022
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: May 20, 2022
• Est. primary completion date: April 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

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

Locations

Country	Name	City	State
China	Shanghai Pulmonary Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Incidence and grade of adverse events (AEs) and Serious adverse events (SAEs)	AEs and SAEs assessed by NCI-CTCAE v4.03	up to 24 weeks
Primary	Part 2:Objective response rate (ORR) per RECIST 1.1	ORR is defined as the proportion of subjects who have achieved complete response (CR) or partial response (PR) according to RECIST 1.1	Up to approximately 6 months
Secondary	Part 1: Apatinib plasma concentrations and serum SHR-1210 concentrations	Apatinib plasma concentrations and serum SHR-1210 concentrations in Expansion cohort	Cycles 1-2(each cycle is 28 days)
Secondary	Part 1:Peak Plasma Concentration (Cmax) of Apatinib and SHR-1210	Cmax of Apatinib and SHR-1210 in Expansion cohort	Cycles 1-2(each cycle is 28 days)
Secondary	Part 1:Objective response rate (ORR) - RECIST 1.1	ORR is defined as the proportion of subjects who have achieved complete response (CR) or partial response (PR) according to RECIST 1.1	Up to approximately 6 months
Secondary	Duration of Response (DoR)	Duration of Response (DoR) per RECIST 1.1	Up to approximately 2 years
Secondary	Progression-free survival(PFS)	PFS per RECIST 1.1	Up to approximately 2 years
Secondary	Overall survival rate at 12 months (OSR12)	OSR12 will be calculated based on Kaplan-Meier estimates of Overall survival at 12 months	Up to approximately 1 years
Secondary	Part 1: Area under the plasma concentration-time curve from time 0 to 24 hrs, AUC[0-24]	AUC[0-24] of Apatinib and SHR-1210 in Expansion cohort	Cycles 1-2(each cycle is 28 days)