Neoplasms

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Lung Neoplasms

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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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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
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

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