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

NCT05021328 | Completed Phase 1

• 1 other identifier: HBCH-RT-2021-01
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

NSCLC

Keywords

Brain metastasis; Toripalimab; Anlotinib; SBRT; Drive gene negative

Outcome Measures

Primary Outcomes (2)

• Treatment-related adverse events

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

  up to 24 month

• Intracranial response rate (iORR)

  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).

  4 weeks after Radiotherapy.

Secondary Outcomes (3)

• Intracranial progression-free survival (iPFS)

  Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months

• Local Control Rate (LCR)

  Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months

• Overall survival (OS)

  Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months

Study Arms (2)

Anlotinib combined with SBRT

EXPERIMENTAL

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)

Drug: Anlotinib; Drug: SBRT 7Gy✖️5 QD

Anlotinib combined with SBRT and Toripalimab

EXPERIMENTAL

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)

Drug: Toripalimab; Drug: Anlotinib; Drug: SBRT 7Gy✖️5 QD

Interventions

Toripalimab DRUG

Toripalimab 240mg, ivgtt, d1, q3w.

Also known as: JS001, Toripalimab Injection, Teruipuli dankang Zhusheye, TuoYI

Anlotinib combined with SBRT and Toripalimab

Anlotinib DRUG

Anlotinib 12 mg/d, d1-14, q3w.

Also known as: AL3818, Anlotinib Hydrochloride Capsules, FuKeWei

Anlotinib combined with SBRT; Anlotinib combined with SBRT and Toripalimab

SBRT 7Gy✖️5 QD DRUG

SBRT 7Gy✖️5 QD

Anlotinib combined with SBRT; Anlotinib combined with SBRT and Toripalimab

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years, no gender limit；
• Pathologically or cytologically confirmed NSCLC, stage IV tumor with untreated BMs diagnosed by imaging 2 weeks before enrollment, 1\~5 intracranial metastases (The primary tumor disease has not received systemic treatment, or brain metastasis occurs 6 months after the completion of postoperative adjuvant treatment or radical treatment);
• Negative driver genes (EGFR, ALK, ROS1, etc.);
• ECOG PS score: 0～1;
• The expected survival time ≥ 3 months;
• Intracranial metastases can be measured and evaluated by MRI;
• Intracranial lesions are suitable for stereotactic radiotherapy based on the linear accelerator;
• Able to independently complete neurocognitive tests;
• Able to complete the QOL questionnaire independently;
• Female subjects with fertility should undergo a urine or serum pregnancy test within 72 hours before receiving the first study drug administration, and prove to be negative, and are willing to use effectively during the test period to 3 months after the last administration Methods of contraception. For male subjects whose partners are women of childbearing age, effective methods of contraception should be used during the trial and within 3 months after the last administration;
• The functions of important organs meet the following requirements (no blood components and cell growth factors are allowed to be used 2 weeks before the start of the research treatment): Absolute Neutrophil Count (ANC) ≥1.5×10 E+9/L, Hemoglobin (HB) ≥9g/dL, Platelets (PLT)≥90×10 E+9/L, Serum Albumin (ALB)≥2.8g/dL, Total Bilirubin (TBIL) ≤1.5 ULN, ALT、AST≤2.5 UILN(If abnormal liver function is caused by liver metastasis, ≤5 ULN), Serum creatinine sCr≤1.5 ULN, endogenous creatinine clearance ≥50ml/min (Cockcroft-Gault formula) , Normal thyroid function;
• The patients joined the study voluntarily and signed an informed consent form (ICF). They had good compliance and cooperated with follow-up.

You may not qualify if:

• The lesion has received prior radiotherapy and is not suitable for SBRT;
• Have leptomeningeal metastasis;
• EGFR, ALK or ROS1 genomic tumour alterations;
• Patients who cannot undergo MRI examination due to metal implants or claustrophobia;
• Currently participating in interventional clinical research and treatment, or receiving other research drugs or treatment with research equipment within 4 weeks before the first administration;
• Accept solid organ or blood system transplantation;
• Past treatment history of CTLA-4, PD-1 or PD-L1 immune checkpoint inhibitors;
• Has received VEGF pathway targeted therapy including anlotinib and bevacizumab.
• Suffer from active autoimmune diseases that require hormone or immunomodulatory treatment, such as rheumatoid arthritis, ankylosing spondylitis, type I diabetes, psoriasis, vitiligo, immune-related thyroid dysfunction, etc. (hormone replacement Can be included after treatment is normal);
• Suffer from acute or chronic infectious diseases, such as hepatitis B, hepatitis C, tuberculosis, and HIV;
• Allergic to research drug ingredients
• Active infection or fever of unknown cause occurred during the screening period and before the first administration\> 38.5℃ (according to the judgment of the investigator, the subject can be included in the group due to fever caused by the tumor);
• Suffer from uncontrolled clinical symptoms or diseases of the heart, such as:(1) Heart failure above NYHA II; (2) Unstable angina pectoris; (3) Myocardial infarction occurred within 1 year; (4) Patients with clinically significant supraventricular or ventricular arrhythmia requiring clinical intervention;
• Suffer from high blood pressure and cannot be well controlled by antihypertensive medication (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg);
• Abnormal blood coagulation function (INR\>2.0, PT\>16s), have a bleeding tendency or are receiving thrombolytic therapy, and allow preventive use of low-dose aspirin and low-molecular-weight heparin;

Sponsors & Collaborators

• Hubei Cancer Hospital: lead

Study Sites (1)

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

toripalimab; anlotinib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: August 25, 2021
• Study Start: October 1, 2021
• Primary Completion: February 5, 2025
• Study Completion: February 5, 2025
• Last Updated: February 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)