Camrelizumab Combined With Apatinib Mesylate or Camrelizumab Alone for First-line Treatment in Subjects With Programmed Death Ligand 1 (PD-L1) Positive Relapsed or Advanced Non-small Cell Lung Cancer (NSCLC)

A Randomized, Open-Label, Controlled, Multicenter Phase III Study of Camrelizumab Combined With Apatinib Mesylate or Camrelizumab Alone Versus Platinum-based Chemotherapy for First-line Treatment in Subjects With PD-L1 Positive Relapsed or Advanced NSCLC

The study is being conducted to evaluate the efficacy and safety of Camrelizumab (200mg,q2w) combined with Apatinib(250mg qd) in subjects with PD-L1 positive relapsed or advanced non-small cell lung cancer.

Study Overview

• Status: Unknown
• Conditions: PD-L1 Positive Non-small Cell Lung Cancer
• Intervention / Treatment: Biological: Camrelizumab 200mg; Drug: Apatinib Mesylate 250mg; Drug: Pemetrexed disodium for injection; Drug: Paclitaxel injection; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Anticipated): 762
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Quanren Wang, PhD; Phone Number: 18036618570; Email: wangquanren@hrglobe.cn
• Study Contact Backup: Name: Weixia Li, Master; Phone Number: 15005136260; Email: liweixia@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 who have recurrent or advanced (Stage IIIB-IV) non-small cell lung cancer confirmed by histology or cytology.
2. No prior systemic treatment. Subjects who have received prior neo-adjuvant, adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment free interval of at least 6 months from randomization since the last chemotherapy cycle.
3. Subjects should not have a previously detected activating Epidermal Growth Factor Receptor (EFGR) mutation or Anaplastic Lymphoma Kinase (ALK) fusion oncogene.
4. Subjects must have measurable disease by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) per RECIST 1.1 criteria;
5. Freshly acquired samples or archived specimens within 6 months before randomization must be provided.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Exclusion Criteria:

1. Radiologically confirmed central squamous cell carcinoma.
2. Untreated central nervous system metastases (such as brain or meningeal metastases).
3. Pleural effusion, pericardial effusion, or ascites with clinical symptoms that need drainage
4. Past or present with idiopathic pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, tissue pneumonia (eg bronchitis, occlusive vasculitis), drug-induced pneumonia, active pneumonia during CT screening, or objective evidence of severe impairment of lung function
5. Subjects with an active, known or suspected autoimmune disease. Patients with type I diabetes who are receiving a stable dose of insulin, hypothyroidism who only needs hormone replacement therapy, and skin diseases (such as eczema, vitiligo, or psoriasis) that do not require systemic treatment and do not have acute deterioration within 1 year before the screening period, are allowed.
6. Subjects with suspected active tuberculosis should be examined for chest X-rays, sputum, and ruled out by clinical signs and symptoms.
7. Uncontrolled Cardiac Symptoms or Diseases.
8. Subjects with high blood pressure who cannot be controlled well with antihypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg).
9. Arterial / venous thrombosis events, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism, occurred within the first 6 months of randomization.
10. Subjects who have previously received anti-PD-1 / PD-L1 monoclonal antibody, anti-cytotoxic T lymphocyte antigen-4 monoclonal antibody, or vascular endothelial growth factor receptor (VEGFR) small molecule inhibitor therapy.

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: Camrelizumab 200mg + Apatinib Mesylate 250mg; Camrelizumab 200mg q2w ivgtt+ Apatinib Mesylate 250mg once daily po qd	Biological: Camrelizumab 200mg; Camrelizumab 200mg q2w ivgtt; Drug: Apatinib Mesylate 250mg; Apatinib Mesylate 250mg po qd
Experimental: Camrelizumab 200mg; Camrelizumab 200mg q2w ivgtt	Biological: Camrelizumab 200mg; Camrelizumab 200mg q2w ivgtt
Active Comparator: Pemetrexed/Paclitaxel injection+ Carboplatin; For non-squamous NSCLC: Pemetrexed disodium for injection + Carboplatin; For squamous NSCLC: Paclitaxel injection + Carboplatin	Drug: Pemetrexed disodium for injection; Pemetrexed disodium for injection 500 mg/m2 q3w; Drug: Paclitaxel injection; Paclitaxel injection 175 mg/m2 q3w; Drug: Carboplatin; Carboplatin AUC 5 mg/mL/min q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) assessed by Independent review committee (IRC)	Progression Free Survival, defined as the time from randomization to the first occurrence of disease progression as determined by IRC with use of Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or death from any cause, whichever occurs first.	up to 2 years
Overall survival	Overall survival is the time interval from the date of randomization to death due to any reason or lost of follow-up	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS assessed by investigator	Progression-Free-Survival	up to 2 years
Objective Response Rate	Objective Response Rate, determined using RECIST v1.1 criteria, defined as best overall response (complete or partial response) across all assessment time points	At the time point of every 6 weeks，up to 2 years
Disease Control Rate	Disease Control Rate, determined using RECIST v1.1 criteria	At the time point of every 6 weeks，up to 2 years
Duration of Response	Duration of Response, determined using RECIST v1.1 criteria	Up to 2 years
Time to Treatment Failure	Time to Treatment Failure, defined as the time from randomization to treatment discontinuation.	Up to 2 years
Adverse Events and Serious Adverse Events	Adverse Events and Serious Adverse Events	from the first drug administration to within 90 days for the last Camrelizumab dose

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Publications and helpful links

General Publications

• Zhou C, Wang Y, Zhao J, Chen G, Liu Z, Gu K, Huang M, He J, Chen J, Ma Z, Feng J, Shi J, Yu X, Cheng Y, Yao Y, Chen Y, Guo R, Lin X, Wang Z, Gao G, Wang Q, Li W, Yang X, Wu L, Zhang J, Ren S. Efficacy and Biomarker Analysis of Camrelizumab in Combination with Apatinib in Patients with Advanced Nonsquamous NSCLC Previously Treated with Chemotherapy. Clin Cancer Res. 2021 Mar 1;27(5):1296-1304. doi: 10.1158/1078-0432.CCR-20-3136. Epub 2020 Dec 15.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 15, 2020
• Primary Completion (Anticipated): March 31, 2022
• Study Completion (Anticipated): May 31, 2022

Study Registration Dates

• First Submitted: December 13, 2019
• First Submitted That Met QC Criteria: December 16, 2019
• First Posted (Actual): December 18, 2019

Study Record Updates

• Last Update Posted (Actual): May 8, 2020
• Last Update Submitted That Met QC Criteria: May 7, 2020
• Last Verified: May 1, 2020

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; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Folic Acid Antagonists; Carboplatin; Paclitaxel; Pemetrexed; Apatinib
• Other Study ID Numbers: SHR-1210-III-315

Drug and device information, study documents

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