Clinical trial NCT04203485: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: PD-L1 Positive Non-small Cell Lung Cancer
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-12-18
Enrollment: 762
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival (PFS) assessed by Independent review committee (IRC)
timeFrame: up to 2 years
measure: Overall survival
timeFrame: up to 2 years
Secondary outcomes:
measure: PFS assessed by investigator
timeFrame: up to 2 years
measure: Objective Response Rate
timeFrame: At the time point of every 6 weeks，up to 2 years
measure: Disease Control Rate
timeFrame: At the time point of every 6 weeks，up to 2 years
measure: Duration of Response
timeFrame: Up to 2 years
measure: Time to Treatment Failure
timeFrame: Up to 2 years
measure: Adverse Events and Serious Adverse Events
timeFrame: from the first drug administration to within 90 days for the last Camrelizumab dose
Other outcomes:
Locations:
Study officials:
References:
citation: 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.