NSCLCPhase 1NCT05021328
Toripalimab Combined With Anlotinib and SBRT in Patients With Untreated Brain Metastases of Driven Gene-negative NSCLC
A Phase 1 study testing Toripalimab, Anlotinib and SBRT 7Gy✖️5 QD in people with NSCLC, run by Hubei Cancer Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC
- What is being tested?
- Toripalimab, Anlotinib and SBRT 7Gy✖️5 QD
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2021to 5 Feb 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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;
- Obvious coughing up blood or hemoptysis of 10ml or more per day in the 2 months before enrollment;
- Have significant clinically significant bleeding symptoms or have a clear bleeding tendency within 3 months before enrollment;
- Have received anti-tumor monoclonal antibodies (mAb) within 4 weeks before using the study drug for the first time, or the adverse events caused by the previously received drug have not recovered (ie ≤ grade 1 or reached the baseline level). Note: Except for subjects with ≤ Grade 2 neuropathy or ≤ Grade 2 hair loss, if the subject has undergone major surgery, the toxic reaction and/or complications caused by the surgical intervention must be fully recovered before starting treatment;
- Live vaccines have been vaccinated within 4 weeks before the first use of the study drug. Inactivated virus vaccines for seasonal influenza and injections are allowed, but live attenuated influenza vaccines for nasal use are not allowed;
- The investigator judged other situations not suitable for inclusion in this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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.
Read the detailed description
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.
- Conditions
- NSCLC
- Being tested
- Toripalimab, Anlotinib, SBRT 7Gy✖️5 QD
- Keywords
- Brain metastasis, Toripalimab, Anlotinib, SBRT, Drive gene negative
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToripalimabDrug
Also called JS001, Toripalimab Injection, Teruipuli dankang Zhusheye, TuoYI
Toripalimab 240mg, ivgtt, d1, q3w.
AnlotinibDrug
Also called AL3818, Anlotinib Hydrochloride Capsules, FuKeWei
Anlotinib 12 mg/d, d1-14, q3w.
SBRT 7Gy✖️5 QDDrug
SBRT 7Gy✖️5 QD
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Drug: Toripalimab; Drug: Anlotinib; Drug: SBRT 7Gy✖️5 QD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-related adverse events
AEs per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Measured: 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).
Measured: 4 weeks after Radiotherapy.
Secondary outcomes (3)
Intracranial progression-free survival (iPFS)
Defined as the time from randomisation to progression of intracranial disease or death from any cause.
Measured: Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months
Local Control Rate (LCR)
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.
Measured: Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months
Overall survival (OS)
Defined as the time from randomisation to death from any cause
Measured: Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2021
- Study start1 Oct 2021
- Primary completion5 Feb 2025
- Study completion5 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hubei Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, HAN GUANG, Hubei Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05021328
- Sponsor's protocol ID
- HBCH-RT-2021-01
- Status last verified
- Feb 2025
- First submitted
- 20 Aug 2021
- Last updated
- 7 Feb 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05021328
- Acronym / sponsor ID
- HBCH-RT-2021-01
- Conditions
- NSCLC
- Keywords
- Brain metastasis, Toripalimab, Anlotinib, SBRT, Drive gene negative
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Hubei Cancer HospitalUniversity, hospital or other
- Study start
- 1 Oct 2021 (actual)
- Primary completion
- 5 Feb 2025 (actual)
- Study completion
- 5 Feb 2025 (actual)
- First posted
- 25 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anlotinib combined with SBRT | Experimental | Drug: Anlotinib, Drug: SBRT 7Gy✖️5 QDInduction 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) |
| Anlotinib combined with SBRT and Toripalimab | Experimental | Drug: Toripalimab, Drug: Anlotinib, Drug: SBRT 7Gy✖️5 QDInduction 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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;
Key exclusion criteria (20 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ToripalimabAlso: JS001, Toripalimab Injection, Teruipuli dankang Zhusheye, TuoYIToripalimab 240mg, ivgtt, d1, q3w. | Drug | Anlotinib combined with SBRT and Toripalimab |
| AnlotinibAlso: AL3818, Anlotinib Hydrochloride Capsules, FuKeWeiAnlotinib 12 mg/d, d1-14, q3w. | Drug | Anlotinib combined with SBRT, Anlotinib combined with SBRT and Toripalimab |
| SBRT 7Gy✖️5 QDSBRT 7Gy✖️5 QD | Drug | Anlotinib combined with SBRT, Anlotinib combined with SBRT and Toripalimab |
Primary outcome
Treatment-related adverse events
Time frame: up to 24 month
AEs per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Intracranial response rate (iORR)
Time frame: 4 weeks after Radiotherapy.
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).
3 secondary outcomes
Intracranial progression-free survival (iPFS)
Time frame: Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months
Local Control Rate (LCR)
Time frame: Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months
Overall survival (OS)
Time frame: Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Toripalimab, Anlotinib and SBRT 7Gy✖️5 QD in people with NSCLC, run by Hubei Cancer Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-related adverse events (time frame: up to 24 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2025.