Phase II Study of SHR-1210(Anti-PD-1 Antibody) Combination With Apatinib Versus Pemetrexed and Carboplatin in Subjects With KRAS Mutant Stage IV Non-squamous Non-small Cell Lung Cancer

This is a randomized, open-label, multi-center, phase II trial to evaluate the efficacy and safety of SHR-1210 plus apatinib mesylate versus Pemetrexed and Carboplatin in Subjects with KRAS mutant stage IV non-squamous Non-small Cell Lung Cancer

Study Overview

• Status: Unknown
• Conditions: Chemotherapy Effect; KRAS Gene Mutation; NSCLC Stage IV; PD-1 Antibody
• Intervention / Treatment: Drug: SHR-1210; Drug: Apatinib; Drug: Pemetrexed; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Anticipated): 230
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jianjun Zou, MD, PhD; Phone Number: 021-60453139; Email: zoujianjun@hrglobe.cn
• Study Contact Backup: Name: ChengLei qiao, PM; Email: qiaochenglei@hrglobe.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subjects with histopathological diagnosis of adenocarcinoma non-small cell lung cancer (NSCLC) and clinical stage IV
2. has not received prior systemic treatment for metastatic NSCLC.
3. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
4. confirmes by the central laboratory as KRAS gene mutation
5. Has archived Tumor tissue samples
6. Subject must have a measurable target lesion based on RECIST v1.1 .
7. Women of childbearing age must undergo a serological pregnancy test within 3 days before the first dose with negative results. Female subjects of reproductive age and male subjects whose spouse is a woman of reproductive age must agree to effective contraception within 180 days after the study period and the last dose of the study drug.
8. Subjects should be voluntarily participate in clinical studies and informed consent should be signed.

Exclusion Criteria:

1. active brain metastases and meningeal metastasis
2. uncontrollable tumor-related pain
3. massive pleural effusion, peritoneal effusion or pericardial effusion which cannot be controlled by repeated drainage;
4. radiotherapy to lung that is >30 Gy within 24 weeks before the first dose,
5. imaging (CT or MRI) showed that the tumor invading the large vessels
6. Known EGFR/ALK mutation.
7. subjects with any known or suspected autoimmune diseases
8. subjects with known or suspected interstitial pneumonia;
9. Subjects with severe cardiovascular and cerebrovascular diseases
10. arteriovenous thrombosis events, such as deep vein thrombosis and pulmonary embolism, occurred within 3 months;
11. female subjects who are pregnant or lactation or who plan to be pregnant during the study period;
12. positive HIV test;
13. active hepatitis B
14. evidence of active TB infection within 1 year before first dose;
15. severe infection occurred within 4 weeks before the first dose
16. patients with clinically significant bleeding symptoms or with obvious bleeding tendency in the first month
17. subjects who is on systemic immunogenic agents;
18. a history of severe allergic reactions to other monoclonal antibodies/fusion proteins;
19. History of severe allergic reactions to carboplatin or pemetrexed or their preventive drugs;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-1210 +apatinib; subject will receive SHR-1210 200mg every 2 weeks, apatinib 250mg every day	Drug: SHR-1210; Subjects receive SHR-1210 intravenous every 2 weeks; Drug: Apatinib; Subjects receive Apatinib orally every day
Active Comparator: chemotherapy; Pemetrexed 500mg/m2, Day 1 of each 21 day, 4 cycles carboplatin AUC 5 on Day 1 of each 21 day, 4 cycles followed by pemetrexed 500mg/m2 until progression Q3W	Drug: Pemetrexed; Subjects receive Pemetrexed intravenous every 3 weeks; Drug: Carboplatin; subjects receive carboplatin intravenous every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Progression-Free Survival (PFS) as Assessed by the Independent Review Committee Using RECIST v1.1	PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the Independent Review Committee Using RECIST v1.1 or death from any cause, whichever occurs first. Patients who have not experienced disease progression or death at the time of analysis will be censored at the time of last tumor assessment.	up to approximately 40 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1	Time Frame: Baseline until PD or death, whichever occurs first	up to approximately 40 months
Duration of Overall Survival (OS)	Baseline until death from any cause	up to approximately 40 months
Objective Response Rate (ORR)	The percentage of patients with CR and PR assessed by investigators according to Recist v 1.1.	up to approximately 40 months
disease control rate (DCR)	The proportion of patients who have achieved complete response， partial response and Stable disease assessed by investigators according to Recist v 1.1.	up to approximately 40 months
Duration of response （DoR）	Duration of response （DoR）	up to approximately 40 months
Adverse events (AEs)	All adverse event/Serious adverse event that occurred during the study period according to CTCAE v 5.0	up to approximately 40 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Collaborators: Shanghai Chest Hospital
• Investigators: Study Director: Jianjun Zou, MD, PhD, Jiangsu HengRui Medicine Co., Ltd.; Principal Investigator: Shun Lu, MD, PhD, Jiaotong University,Shanghai chest Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2019
• Primary Completion (Anticipated): April 1, 2020
• Study Completion (Anticipated): April 1, 2022

Study Registration Dates

• First Submitted: December 13, 2018
• First Submitted That Met QC Criteria: December 13, 2018
• First Posted (Actual): December 17, 2018

Study Record Updates

• Last Update Posted (Actual): January 18, 2019
• Last Update Submitted That Met QC Criteria: January 17, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Carboplatin; Pemetrexed; Apatinib
• Other Study ID Numbers: SHR-1210-II-214

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