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

NCT ID: NCT03083041

Last Updated: 2023-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-22
• Study Completion Date: 2022-05-20

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.

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SHR-1210，200mg,q2w plus apatinib 250mg/d

SHR-1210 200mg, IV, Q2W and Apatinib 250mg, PO, QD

Group Type: EXPERIMENTAL

SHR-1210

Intervention Type: BIOLOGICAL

SHR-1210 will be administered as a 30-minute IV infusion Q2W at a dose of 200mg

Apatinib

Intervention Type: DRUG

Apatinib tablet will be administered orally,once daily until progression

SHR-1210，200mg,q2w plus apatinib 500mg/d

SHR-1210 200mg, IV, Q2W and Apatinib 500mg, PO, QD

Group Type: EXPERIMENTAL

SHR-1210

Intervention Type: BIOLOGICAL

SHR-1210 will be administered as a 30-minute IV infusion Q2W at a dose of 200mg

Apatinib

Intervention Type: DRUG

Apatinib tablet will be administered orally,once daily until progression

SHR-1210，200mg,q2w plus apatinib 375mg/d

SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD

Group Type: EXPERIMENTAL

SHR-1210

Intervention Type: BIOLOGICAL

SHR-1210 will be administered as a 30-minute IV infusion Q2W at a dose of 200mg

Apatinib

Intervention Type: DRUG

Apatinib tablet will be administered orally,once daily until progression

Interventions

SHR-1210

SHR-1210 will be administered as a 30-minute IV infusion Q2W at a dose of 200mg

Intervention Type: BIOLOGICAL

Apatinib

Apatinib tablet will be administered orally,once daily until progression

Intervention Type: DRUG

Other Intervention Names

Apatinib Mesylate

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu HengRui Medicine Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 35832447 (View on PubMed)

Other Identifiers

SHR-1210-APTN-II-202-NSCLC

Identifier Type: -

Identifier Source: org_study_id