Camrelizumab Combined With SRT/WBRT and Chemotherapy in Patients With Brain Metastases of Driven Gene-negative NSCLC

Randomized, Double-blind, Placebo-controlled, Multi-center Study of Camrelizumab Combined With SRT/WBRT and Chemotherapy in Patients of NSCLC With Brain Metastases of Driven Gene-negative and Not Received Systemic Chemotherapy

This study is a randomized, double-blind, placebo-controlled, multi-center clinical study. Target population is patients with stage IV non-small cell lung cancer who had not received systemic chemotherapy. Study objective is to compare the efficacy and safety of Camrelizumab + carboplatin/cisplatin + pemetrexed /paclitaxel / albumin paclitaxel ± SRT/WBRT with placebo + carboplatin/cisplatin + pemetrexed /paclitaxel / albumin paclitaxel ± SRT/WBRT. Camrelizumab is a humanized anti-PD1 IgG4 monoclonal antibody.

Study Overview

• Status: Completed
• Conditions: Non-Small-Cell Lung Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: Carboplatin; Drug: Pemetrexed; Drug: Cisplatin; Drug: Camrelizumab; Drug: Albumin paclitaxel; Drug: Placebo

Detailed Description

Detailed Description:

In this study, eligible subject will be randomized into study arm or control arm to accept study treatment. Paticipant was confirmed without EGFR activating mutation or ALK fusion and received no prior systemic therapy. Patients would receive Camrelizumab/placebo in combination with chemotherapy for 4-6 cycles，non-squamous subject followed by Camrelizumab/placebo + pemetrexed as maintenance treatment until progression or unacceptable toxicity, squamous subject followed by Camrelizumab/placebo as maintenance treatment until progression or unacceptable toxicity, Camrelizumab/placebo for a maximum of 2 years.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Nanning, China
    • Affiliated Tumor Hospital of Guangxi Medical University
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Beijing Cancer hospital
  • Fuzhou
    • Fujian, Fuzhou, China
      • Fujian Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Guangzhou University of Chinese Medicine
  • Guangxi
    • Nanning, Guangxi, China
      • The First Affiliated Hospital of Guangxi Medical University
  • Hebei
    • Baoding, Hebei, China
      • Affiliated Hospital of Hebei University / School of Clinical Medicine
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Medical College, Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Zhongda Hospital Southeast University
  • Jiangxi
    • Nanchang, Jiangxi, China
      • The Second Affiliated Hospital of Nanchang University
  • Shandong
    • Binzhou, Shandong, China
      • Binzhou Medical University Hospital
  • Shanxi
    • Xi’an, Shanxi, China
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histological or cytological diagnosis of non-small cell lung cancer（NSCLC）;
2. MRI confirmed brain parenchyma metastasis, ≥ 3 brain lesions, or 1-2 brain lesions but not suitable for local treatment or refused local treatment. At least one brain measurable lesion ≥ 5mm . Included with or without neurological symptoms;
3. Has not received prior systemic treatment for metastatic NSCLC. Subjects who have received prior neo-adjuvant, adjuvant chemotherapy, or chemoradiotherapy with curative intent must have experienced interval of at least 12 months from diagnosed of advanced or metastatic disease since the end of surgery;
4. Has confirmation that epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated;
5. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status;
6. Has adequate organ function;
7. Women of childbearing age must undergo a serological pregnancy test within 7 days before the first dose with negative results. Subjects willing to use an effective contraceptive method during the study and within 90 days after the last dose of study medication;
8. Subjects should be able to follow the research and follow-up procedures;
9. Subjects should be voluntarily participating in clinical studies and informed consent should be signed;

Exclusion Criteria:

1. Brain metastases with hemorrhage；
2. Meningeal involvement with metastatic carcinoma;
3. Subjects with ROS1 mutation, RET fusion positive, BRAF V600E mutation, NTRK fusion positive;
4. Participated in other clinical trials, or finish other clinical trials within 4 weeks;
5. Subject was received irradiation of brain;
6. Subjects have received solid organ or blood system transplantation;
7. Active autoimmune diseases requiring systemic treatment (such as the use of disease remission drugs, corticosteroids or immunosuppressants) occurred within 2 years before the first administration. Alternative therapy (such as thyroxine, insulin or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic therapy;
8. Subjects diagnosed immunodeficiency or receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy of non-related tumor within 7 days before the first dose; allowed physiological dose of glucocorticoid (≤10 mg/day Prednisone or equivalent);
9. Within 1 year before the first dose, there was a history of non-infectious pneumonia or interstitial lung disease requiring glucocorticoid treatment;
10. Subjects with grade II or above myocardial ischemia or myocardial infarction and poorly controlled arrhythmias (QTc interval > 450 ms for males and QTc interval > 470 ms for females). Subjects with grade III-IV cardiac insufficiency or with left ventricular ejection fraction (LVEF) less than 50% according to NYHA criteria;
11. Has known history of Human Immunodeficiency Virus (HIV)；
12. Untreated active hepatitis B；
13. Subjects have active hepatitis B；
14. Subjects have severe infections within 4 weeks of the first dose of study treatment；
15. Subjects with clinically significant bleeding symptoms or with obvious bleeding tendency in the first month;
16. Women who are pregnant or lactating；
17. Has known allergy to Camrelizumab, or pemetrexed, or paclitaxel, or albumin paclitaxel, or carboplatin, or cisplatin or any of accessories;
18. A prior malignancy other than NSCLC within 5 years before randomization，except carcinoma in situ of the cervix or basal cell carcinoma or squamous cell carcinoma of skin cancer with adequately treated, localized prostate cancer or ductal carcinoma in situ after radical resection.

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: Camrelizumab group; subject will receive Camrelizumab intravenously(IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by Camrelizumab ± pemetrexed IV Q3W until progression (up to approximately 2 years). Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.	Drug: Paclitaxel; IV infusion; Other Names: Paclitaxel injection; Drug: Carboplatin; IV infusion; Other Names: Carboplat; Drug: Pemetrexed; IV infusion; Other Names: Pemetrexed disodium; Drug: Cisplatin; IV infusion; Other Names: cisplatinum; Drug: Camrelizumab; Camrelizumab is a humanized anti-PD1 IgG4 monoclonal antibody; Other Names: SHR-1210; Drug: Albumin paclitaxel; IV infusion; Other Names: Nab-paclitaxel
Placebo Comparator: placebo group; subject will receive placebo intravenously (IV) PLUS pemetrexed or paclitaxel or albumin paclitaxel PLUS cisplatin or carboplatin AUC 5 on Day 1 of each 3-week cycle(Q3W) for 4-6 cycles followed by placebo ± pemetrexed IV Q3W until progression (up to approximately 2 years). Whether the subject accepts intracranial radiotherapy will be decided by investigators according to the guidelines and the conditions of the subjects.	Drug: Paclitaxel; IV infusion; Other Names: Paclitaxel injection; Drug: Carboplatin; IV infusion; Other Names: Carboplat; Drug: Pemetrexed; IV infusion; Other Names: Pemetrexed disodium; Drug: Cisplatin; IV infusion; Other Names: cisplatinum; Drug: Albumin paclitaxel; IV infusion; Other Names: Nab-paclitaxel; Drug: Placebo; IV infusion Simulator of Camrelizumab; Other Names: Simulator of Camrelizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial Progression-Free Survival(iPFS)	Intracranial Progression-free survival is defined as the duration from date of enrollment to the first occurrence of progression in brain metastasis disease or death from any cause or switch therapy	up to 24 months
Progression-Free Survival (PFS)	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first.	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial Objective Response Rate (iORR)	iORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response(PR: ≥30% decrease in the sum of diameters of target lesions) in brain lesion per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	up to 24 months
Objective Response Rate (ORR)	ORR was defined as the percentage of participants in the analysis population who had a CR or a PR.	up to 24 months
Intracranial Duration of Response (iDOR)	iDOR was defined as the time from first documented evidence of a CR or PR until PD or death	up to 24 months
Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause.	up to death
Duration of Response (DOR)	DOR was defined as the time from first documented evidence of a CR or PR until PD or death	up to 24 months
Adverse events (AEs)/ Serious adverse event (SAE)	All adverse event/Serious adverse event that occurred during the study period according to CTCAE v 5.0	up to 24 months
Mini-Mental State Examination (MMSE)	Assessment of cognitive function using the Mini-Mental State Examination (MMSE). The MMSE evaluates orientation, registration, attention and calculation, recall, and language. Total scores range from 0 to 30, with higher scores indicating better cognitive function.	Assessed at baseline and at each scheduled tumor imaging assessment (every 6 weeks for the first 48 weeks, then every 12 weeks thereafter) up to 24 months
Hopkins Verbal Learning Test - Revised (HVLT-R)	Assessment of verbal learning and memory using the Hopkins Verbal Learning Test - Revised (HVLT-R). The HVLT-R consists of three learning trials of a 12-word list, a delayed recall trial, and a delayed recognition trial. Total recall score (trials 1-3) ranges from 0 to 36, delayed recall score from 0 to 12, and recognition discrimination index from -12 to 12. Higher scores indicate better verbal learning and memory function.	Assessed at baseline and at each scheduled tumor imaging assessment (every 6 weeks for the first 48 weeks, then every 12 weeks thereafter) up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Functioning Scales (EORTC QLQ-C30)	Change from baseline in patient-reported global health status/quality of life, as measured by the EORTC QLQ-C30 global health status/QoL scale. Scores are transformed to a 0-100 scale; higher scores indicate better quality of life.	Assessed at baseline and at each scheduled tumor imaging assessment (every 6 weeks for the first 48 weeks, then every 12 weeks thereafter) up to 24 months

Collaborators and Investigators

• Sponsor: Guangdong Association of Clinical Trials
• Investigators: Principal Investigator: Wu Yi Long, PhD, Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences

Publications and helpful links

General Publications

• Li YS, Yu Q, Bu Q, Lin L, Ning F, Zhao Y, Wu G, Lin G, Zang A, Sun H, Huang J, Tu HY, Ma S, Zhou C, Liu A, Wang C, Yao Y, Han G, Zhao J, Zhou Q, Yan HH, Liu SM, Zheng MM, Lv J, Cheng F, Chen Z, Zhong WZ, Pan Y, Yang JJ, Wu YL. First-Line Camrelizumab Versus Placebo Plus Chemotherapy With or Without Radiotherapy for Brain Metastases in NSCLC: The CTONG 2003 Randomized Placebo-Controlled Trial. J Thorac Oncol. 2025 Jul;20(7):928-940. doi: 10.1016/j.jtho.2025.02.004. Epub 2025 Feb 8.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2021
• Primary Completion (Actual): March 1, 2026
• Study Completion (Actual): April 30, 2026

Study Registration Dates

• First Submitted: February 4, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 24, 2021

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• 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; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Platinum Compounds; Pemetrexed; Carboplatin; Paclitaxel; Cisplatin; 130-nm albumin-bound paclitaxel; camrelizumab
• Other Study ID Numbers: CTONG2003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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