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

NCT04768075 | Unknown Phase 3

• 1 other identifier: CTONG2003
• Study Type: interventional
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Non-Small-Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 month

Secondary Outcomes (9)

• Intracranial Objective Response Rate (iORR)

  up to 24 month

• Objective Response Rate (ORR)

  up to 24 month

• Progression-Free Survival (PFS)

  up to 24 month

• Overall Survival (OS)

  up to 24 month

• Duration of Response (DOR)

  up to 24 month

Study Arms (2)

Camrelizumab group

EXPERIMENTAL

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: Camrelizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Albumin paclitaxel

placebo group

PLACEBO COMPARATOR

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: Placebo; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Albumin paclitaxel

Interventions

Camrelizumab DRUG

Camrelizumab is a humanized anti-PD1 IgG4 monoclonal antibody

Also known as: SHR-1210

Camrelizumab group

Placebo DRUG

IV infusion Simulator of Camrelizumab

Also known as: Simulator of Camrelizumab

placebo group

Cisplatin DRUG

IV infusion

Also known as: cisplatinum

Camrelizumab group; placebo group

Carboplatin DRUG

IV infusion

Also known as: Carboplat

Camrelizumab group; placebo group

Pemetrexed DRUG

IV infusion

Also known as: Pemetrexed disodium

Camrelizumab group; placebo group

Paclitaxel DRUG

IV infusion

Also known as: Paclitaxel injection

Camrelizumab group; placebo group

Albumin paclitaxel DRUG

IV infusion

Also known as: Nab-paclitaxel

Camrelizumab group; placebo group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytological diagnosis of non-small cell lung cancer（NSCLC）;
• 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;
• 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;
• Has confirmation that epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated;
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status;
• Has adequate organ function;
• 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;
• Subjects should be able to follow the research and follow-up procedures;
• Subjects should be voluntarily participating in clinical studies and informed consent should be signed;

You may not qualify if:

• Brain metastases with hemorrhage；
• Meningeal involvement with metastatic carcinoma;
• Subjects with ROS1 mutation, RET fusion positive, BRAF V600E mutation, NTRK fusion positive;
• Participated in other clinical trials, or finish other clinical trials within 4 weeks;
• Subject was received irradiation of brain;
• Subjects have received solid organ or blood system transplantation;
• 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;
• 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);
• Within 1 year before the first dose, there was a history of non-infectious pneumonia or interstitial lung disease requiring glucocorticoid treatment;
• 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;
• Has known history of Human Immunodeficiency Virus (HIV)；
• Untreated active hepatitis B；
• Subjects have active hepatitis B；
• Subjects have severe infections within 4 weeks of the first dose of study treatment；
• Subjects with clinically significant bleeding symptoms or with obvious bleeding tendency in the first month;

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead

Related Publications (1)

• 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.

  PMID: 39929333 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

camrelizumab; Cisplatin; Carboplatin; Pemetrexed; Paclitaxel; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Wu Yi Long, PhD

  Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yang Jin-Ji, MD

CONTACT

+86 20 83827812; Yangjinji2003@163.com

Wu Yi-Long, PhD

CONTACT

+86 20 83827812; syylwu@live.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2021
• First Posted: February 24, 2021
• Study Start: March 5, 2021
• Primary Completion: April 30, 2022
• Study Completion: April 30, 2024
• Last Updated: February 24, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share