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

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

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Biological: SHR-1210; Drug: Apatinib

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
• Enrollment (Actual): 210
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200433
      • Shanghai Pulmonary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: Apatinib Mesylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Grade of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of participants with Adverse Events and Serious Adverse Events	from signing the informed consent form to safety follow-up, 61 months
Objective Response Rate (ORR)：	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	from first administration to progressive disease or initiation of new anti-cancer therapy, 61 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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
Duration of Response (DoR)	Duration of Response (DoR) per RECIST 1.1	Up to approximately 2 years
Progression-free survival(PFS)	PFS per RECIST 1.1	Up to approximately 2 years
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
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)

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2017
• Primary Completion (Actual): April 22, 2022
• Study Completion (Actual): April 22, 2022

Study Registration Dates

• First Submitted: March 2, 2017
• First Submitted That Met QC Criteria: March 13, 2017
• First Posted (Actual): March 17, 2017

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: NSCLC; Apatinib; SHR-1210
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; camrelizumab; apatinib
• Other Study ID Numbers: SHR-1210-APTN-II-202-NSCLC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No