Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Lung Neoplasms

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Induction therapy (D1-D21): SBRT 7Gy✖️5 QD, D1-D5 + Toripalimab 240mg iv drip D1 + Anlotinib 12mg, QD, PO, D1-D14；

Maintenance (D22\~1year): Toripalimab 240mg iv drip D1 Q3W + Anlotinib 12mg, QD, PO, D1-D14, Q3W, until progression (up to approximately 1 year)

Induction therapy (D1-D21): SBRT 7Gy✖️5 QD, D1-D5 + Anlotinib 12mg, QD, PO, D1-D14；

Maintenance (D22\~1year): Toripalimab 240mg iv drip D1 Q3W + Anlotinib 12mg, QD, PO, D1-D14, Q3W, until progression (up to approximately 1 year)

Toripalimab

Anlotinib

SBRT 7Gy✖️5 QD

Guang Han, MD

Han Guang, MD

The purpose of this study is to explore the efficacy and safety of toripalimab combined with anlotinib and SBRT for non-driver gene mutation untreated brain metastases non-small Cell Lung Cancer.

Brain metastases (BM) develop in 22-54% of NSCLC patients during the disease course. NSCLC patients with BM with a median overall survival (OS) of 2-3 months when treated with systemic corticosteroid alone, and a median OS of 10-12 months when treated with brain radiation therapy. Recently, several studies have reported the benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for EGFR mutation NSCLC patients with BM. The median OS of EGFR mutation patients with BM significantly improved with TKIs treatment, which ranged from 11.8 to 18.8 months. However, for the EGFR wide-type NSCLC patients with BM, the prognosis remains poor.

JS-001 is the first monoclonal antibody (mAb) against programmed cell death protein-1 (PD-1) approved by the China Food and Drug Administration (CFDA) into the clinical trails.

Anlotinib hydrochloride is a multi-target receptor tyrosine kinase inhibitor that has significant inhibitory activity against angiogenesis related kinases such as VEGFR1/2/3, FGFR1/2/3, and other tumor related kinases such as PDGFR /, C-Kit, Ret, etc. (e.g., Met, FGFR1/2/3).

The previously study (2021 EMSO congress abstract) found that Apatinib, another kind of tyrosine kinase inhibitor that selectively inhibits the VEGFR-2, combined with brain radiation therapy could improve mOS time to 17 months in lung cancer patients with BMs.

Therefore, the investigators initiated this study to evaluate the efficacy and safety of toripalimab combined with anlotinib and SBRT for non-driver gene mutation untreated brain metastases non-small Cell Lung Cancer.

Toripalimab Combined With Anlotinib and SBRT in Patients With Untreated Brain Metastases of Driven Gene-negative NSCLC

A Phase Ib Study on Toripalimab Combined With Anlotinib and SBRT for Patients With Untreated Brain Metastases of Driven Gene-negative Non-small Cell Lung Cancer

AEs per Common Terminology Criteria for Adverse Events (CTCAE V5.0)

Proportion of patients with a complete or partial response in intracranial metastases as measured using RECIST 1.1 criteria (modified for brain metastases - bm RECIST).

Defined as the time from randomisation to progression of intracranial disease or death from any cause.

Local recurrence is defined as the onset or progression of nodular contrast grafting within the resection cavity according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.

Defined as the time from randomisation to death from any cause

Hubei Cancer Hospital

Clinical Professor

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Apatinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Drugs: Apatinib Apatinib (500 mg/d) was given orally for one week before the brain radiotherapy, and then, continued to be administered at the same way during the brain radiotherapy period (3 weeks). It was given for another one week after the end of the brain radiotherapy.

Radiotherapy: Intensity-modulated radiotherapy (IMRT).

According to the patients KPS score, GPA score, the number and size of metastatic lesions can be selected:

1. 37.5Gy/15 fractions of whole brain irradiation for multiple brain metastases were more than 5;
2. The whole brain was irradiated with 37.5Gy/15 and simultaneous integrated boost dose of 52.5Gy/15 to patients with 1-5 metastatic lesions.

Radiotherapy: Intensity-modulated radiotherapy (IMRT).

According to the patients KPS score, GPA score, the number and size of metastatic lesions can be selected:

1. 37.5Gy/15 fractions of whole brain irradiation for multiple brain metastases were more than 5;
2. The whole brain was irradiated with 37.5Gy/15 and simultaneous integrated boost dose of 52.5Gy /15 to patients with 1-5 metastatic lesions.

Desheng Hu

The purpose of this study is to evaluate the efficacy and safety of concurrent radiotherapy with Apatinib in patients with Brain Metastases from drive gene wide-type Non-small-cell Lung Cancer (NSCLC).

Brain metastases (BM) develop in 22-54% of NSCLC patients during the disease course. NSCLC patients with BM with a median overall survival (OS) of 2-3 months when treated with systemic corticosteroid alone, and a median OS of 3-6 months when treated with whole brain radiation therapy (WBRT). Recently, several studies have reported the benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for EGFR mutation NSCLC patients with BM. The median OS of EGFR mutation patients with BM significantly improved with TKIs treatment, which ranged from 11.8 to 18.8 months. However, for the EGFR wide-type NSCLC patients with BM, the prognosis remains poor.

It was found that the combination of anti-VEGF drugs and brain radiotherapy can not only reduce the volume of peritumoral brain edema (PTBE), reduce the intracranial pressure, relieve the symptoms of nerve compression, reduce the risk of brain hernia during brain radiotherapy, and but also inhibit the hypoxia of tumor cells, increase the radiosensitivity of tumor cells, and ultimately improve the efficacy of radiotherapy.

Apatinib, a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor (VEGFR) and mildly inhibits c-Kit and c-SRC, has been reported to show efficacy among some patients with malignant supratentorial gliomas.

Therefore, the investigators initiated this study to evaluate the efficacy and safety of concurrent radiotherapy with Apatinib in patients with Brain Metastases from drive gene wide-type Non-small-cell Lung Cancer (NSCLC).

Apatinib Combined With Radiotherapy in Patient With BM From Drive Gene Negative NSCLC

A Prospective, Multicenter, Randomized Controlled Trial of Apatinib Combined With Radiotherapy in Patient With Brain Metastases From Drive Gene Negative NSCLC

Proportion of patients with reduction or keeping in stable in tumor burden of a predefined amount

Proportion of patients with reduction in tumor burden of a predefined amount

Defined as the time from randomisation to progression of intracranial disease

PTBE volume was measured in a similar manner by measuring the high SI region in T2WI that was clearly distinguished from normal tissues, including the tumor. Edema index was calculated by dividing the PTBE volume by tumor volume. The Edema index represents the degree of the PTBE, compared to tumor volume, with an index of 1.0 indicating no PTBE development.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Toripalimab Combined With Anlotinib and SBRT in Patients With Untreated Brain Metastases of Driven Gene-negative NSCLC	NCT05021328	NSCLC	Toripalimab Anlotinib SBRT 7Gy✖️5 QD	18 Years -	Hubei Cancer Hospital
Apatinib Combined With Radiotherapy in Patient With BM From Drive Gene Negative NSCLC	NCT03801200	NSCLC	Apatinib	18 Years - 75 Years	Hubei Cancer Hospital
Toripalimab Combined With Anlotinib and SBRT in Patients With Untreated Brain Metastases of Driven Gene-negative NSCLC	NCT05021328	NSCLC	Toripalimab Anlotinib SBRT 7Gy✖️5 QD	18 Years -	Hubei Cancer Hospital

Spots Global Cancer Trial Database for drive gene negative