Non Small Cell Lung CancerPhase 2NCT06702826
Cadonilimab Combined With Stereotactic Radiotherapy as Second-line Treatment for Brain Metastases
A Phase 2 study testing Cadonilimab combined with SRS in people with Non Small Cell Lung Cancer and Brain Metastases, run by Rongrong Zhou at 1 site in China.
Trial summary
The goal of this clinical trial is to evaluate the efficacy and safety of Cadonilimab combined with stereotactic radiation therapy in the second-line treatment of brain metastases from non-small cell lung cancer (NSCLC). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non Small Cell Lung Cancer, Brain Metastases, Stereotactic Radiation
- What is being tested?
- Cadonilimab combined with SRS
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2024to 1 Nov 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years old ≤ 75 years old; Both male and female;
- ECOG 0-1;
- Histologically or cytologically confirmed non-small cell lung cancer;
- Progression with brain metastasis after previous first-line anti-tumor therapy;
- Requirements for brain metastases: ① measurable brain metastases without radiotherapy; ②SRS/FSRT: the maximum tumor volume of brain metastases was less than 10cm3, the single diameter was less than 3cm, and the total volume of brain metastases involved was less than 15 cm3.
- Response to previous checkpoint inhibitor therapy on the initial response assessment;
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- If a metastatic lesion of the head has been irradiated, the cumulative radiation dose does not exceed the tolerated dose to all structures.
- For patients with measurable CNS lesions, the longest diameter on MRI images is ≥10mm, which is suitable for repeated and accurate measurement.
- Subjects were evaluated for all extracranial disease sites (e.g., by computed tomography (CT) scan and bone scan or positron emission tomography (PET-CT) within 14 days before the first dose.
- Subjects had to have a baseline brain MRI scan within 14 days before the first dose of medication.
- Estimated survival time > 12 weeks.
- Participants of childbearing age must agree to use effective contraception during the trial; In women of childbearing age, a serum or urine pregnancy test must be negative.
- Patients who are not lactating.
- Have definite and good organ functions:
- Provide informed consent voluntarily, and be willing and able to comply with the follow-up, treatment, laboratory testing, and other study requirements specified in the study schedule.
Who cannot join
- Subjects who meet any of the following criteria are not eligible to participate in the study:
- Experienced grade 3-4 intracranial toxicity (pituitary or central nervous system toxicity);
- No measurable intracranial metastatic lesions without radiotherapy;
- Meningeal metastasis;
- If receiving chemotherapy or targeted therapy, the washout period should not exceed 3 weeks; if receiving brain metastasis resection, the washout period should not exceed 2 weeks;
- Have significant autoimmune diseases
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- Prior treatment with a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor.
- Previous (within 5 years) or concurrent other malignant tumors
- History of anaphylaxis to any monoclonal antibody and/or study drug component.
- A history of or current noninfectious pneumonia/interstitial lung disease requiring systemic glucocorticoids.
- Serious infection within 4 weeks before the first dose.
- Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
- Subjects required systemic treatment with corticosteroids (>10mg prednisone equivalent per day) or other immunosuppressive drugs within 14 days before taking the study drug.
- Patients with clinically significant cardiovascular disease
- Enroll in another clinical study at the same time, unless it is an observational, noninterventional clinical study or a follow-up of an interventional study.
- Received live vaccine within 30 days before the first dose, or planned to receive live vaccine during the study.
- Known history of mental illness, substance abuse, alcohol or drug abuse.
- Pregnant or lactating women.
- The presence of any past or current medical conditions, treatments, or laboratory abnormalities may confound the results of the study, interfere with the full participation of the subject in the study, or may not be in the best interest of the subject to participate in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Xiangya Hospital, Central South University
Changsha, Hunan
Rongrong Zhou, MD, PHD, +8613875898127, zhourr@csu.edu.cn
About this study
Official title: Efficacy and Safety of Cadonilimab Combined With Stereotactic Radiotherapy as Second-line Treatment for Brain Metastases From Non-small Cell Lung Cancer (NSCLC) : a Single-arm, Open-label, Phase II Clinical Trial
The goal of this clinical trial is to evaluate the efficacy and safety of Cadonilimab combined with stereotactic radiation therapy in the second-line treatment of brain metastases from non-small cell lung cancer (NSCLC).
The main questions it aims to answer are:
- Does Cadonilimab combined with SRT in the second-line treatment of brain metastases provide better results?
- Is the toxicity of Cadonilimab combined with SRT manageable in second-line treatment of brain metastases? Researchers will compare evaluate the efficacy and safety of Cadonilimab combined with SRT as a second-line treatment for patients with advanced NSCLC：
- Receive Cadonilimab combined with SRT for brain lesions.
- Visit the hospital regularly once every 12 weeks for checkups and tests
Read the detailed description
Lung cancer is the cancer with the highest morbidity and mortality in the world. The most common metastatic site of lung cancer is the brain.
Radiotherapy is a classic treatment for brain metastases from lung cancer. Stereotactic radiosurgery (SRS) has image-guided technology, which can accurately find the location of the tumor with an accuracy of millimeters, and effectively reduce the radiation to the surrounding normal tissues. According to the relevant recommendations of the NCCN guidelines for Central nervous System Tumors (first edition 2022), SRS can be given priority to patients with newly diagnosed localized brain metastases or with stable systemic tumor control, which can better protect the cognitive function of patients. SRS should be considered initial therapy in patients with a limited number of brain metastases. Citation (S) : SRS should be considered especially in patients with good physical activity status (PS) and small total tumor volume.
The brain was once considered to be an immune privilege organ, which can actively inhibit any immune response. The 2019 NCCN guidelines have recommended immune checkpoint inhibitors (ICIs) as the first-line treatment for some patients with lung cancer, and the application of ICIs in lung cancer with brain metastases is also being explored. Several phase III RCT studies have shown that immunotherapy prolongs the survival of patients with brain metastases.
As a classic treatment for brain metastases from lung cancer, radiotherapy can promote the anti-tumor immune effect by inducing immunogenic cell death, exposing tumor-associated antigens, activating dendritic cells, changing the tumor microenvironment, and enhancing the expression of intercellular adhesion molecule-1 (ICAM-1), Fas and major histocompatibility complex Ⅰ (MHCⅠ) in tumor cells. High-dose fractionated radiotherapy also has immunogenicity, which may open the blood-brain barrier (BBB) and promote the entry of ICI into brain tissue. However, radiotherapy can up-regulate the expression of PD-L1 and inhibit tumor immunity, which can be improved by ICI. In conclusion, intracranial radiotherapy combined with ICIs has feasibility and theoretical basis for the treatment of malignant tumors.
Cadonilimab is a bispecific antibody (BsAb) that can bind to both PD-1 and CTLA-4 with high affinity. It is a novel tumor immunotherapy drug with a quadrivalent structure and a short half-life, and has been shown to have less toxicity than the combination of anti-PD-1 and anti-CTLA-4 antibodies in monkey toxicity studies. These features make it possible that the use of Cadonilimab in cancer subjects may have better efficacy and safety.
In conclusion, the combination of Cadonilimab with radiotherapy has potential advantages and is expected to have the potential to further improve antitumor efficacy. Therefore, the aim of this study is to evaluate the efficacy and safety of Cadonilimab combined with SRS in the treatment of brain metastases from NSCLC, and to provide evidence for future studies.
- Being tested
- Cadonilimab combined with SRS
- Keywords
- non small cell lung cancer, brain metastases, SRS, immunotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cadonilimab combined with SRSDrug
Eligible subjects were treated with stereotactic radiotherapy for brain metastases plus Cadonilimab followed by maintenance therapy with Cadonilimab alone
| Study group | Role | What they receive |
|---|---|---|
| Cadonilimab combined with SRS | Experimental | Eligible subjects were treated with stereotactic radiotherapy for brain metastases plus Cadonilimab followed by maintenance therapy with Cadonilimab alone Receives: Drug: Cadonilimab combined with SRS |
What is being measured
The primary outcome is the main question the study is designed to answer.
iORR
Intracranial objective response rate (iORR) was defined as the proportion of patients who achieved a prespecified reduction in tumor volume and maintained the minimum time requirement, including CR and PR cases.
Measured: From date of enrollment until the date of first documented intracranial progression, assessed up to 2 years.
Secondary outcomes (3)
PFS
Progression-free survival (PFS) : defined as the time from first use of a study drug to documentation of disease progression (according to RECIST v1.1) or death from any cause, whichever occurred first.
Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.
iPFS
Intracranial Progress Free Survival rate (iPFS) : the time from clinical detection of brain metastases to the first occurrence of intracranial progression or death. iPFS was assessed according to the Response Assessment of Brain Metastases in Neurooncology (RANO-BM) criteria.
Measured: From date of enrollment until the date of first documented intracranial progression or date of death from any cause, whichever came first, assessed up to 2 years
OS
Overall survival (OS) : defined as time from treatment initiation to death from any cause.
Measured: From date of enrollment until the date of death from any cause, whichever came first, assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2024
- Study start1 Nov 2024
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rongrong Zhou
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Rongrong Zhou, Xiangya Hospital of Central South University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06702826
- Sponsor's protocol ID
- 202410188
- Status last verified
- Nov 2024
- First submitted
- 18 Nov 2024
- Last updated
- 25 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Cadonilimab Combined With Stereotactic Radiotherapy as Second-line Treatment for Brain Metastases From Non-small Cell Lung Cancer (NSCLC) : a Single-arm, Open-label, Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT06702826
- Acronym / sponsor ID
- 202410188
- Keywords
- non small cell lung cancer, brain metastases, SRS, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Rongrong ZhouUniversity, hospital or other
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- 1 Nov 2027 (estimated)
- Study completion
- 1 Nov 2027 (estimated)
- First posted
- 25 Nov 2024 (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 goal of this clinical trial is to evaluate the efficacy and safety of Cadonilimab combined with stereotactic radiation therapy in the second-line treatment of brain metastases from non-small cell lung cancer (NSCLC).
The main questions it aims to answer are:
- Does Cadonilimab combined with SRT in the second-line treatment of brain metastases provide better results?
- Is the toxicity of Cadonilimab combined with SRT manageable in second-line treatment of brain metastases? Researchers will compare evaluate the efficacy and safety of Cadonilimab combined with SRT as a second-line treatment for patients with advanced NSCLC：
- Receive Cadonilimab combined with SRT for brain lesions.
- Visit the hospital regularly once every 12 weeks for checkups and tests
Detailed description
Lung cancer is the cancer with the highest morbidity and mortality in the world. The most common metastatic site of lung cancer is the brain.
Radiotherapy is a classic treatment for brain metastases from lung cancer. Stereotactic radiosurgery (SRS) has image-guided technology, which can accurately find the location of the tumor with an accuracy of millimeters, and effectively reduce the radiation to the surrounding normal tissues. According to the relevant recommendations of the NCCN guidelines for Central nervous System Tumors (first edition 2022), SRS can be given priority to patients with newly diagnosed localized brain metastases or with stable systemic tumor control, which can better protect the cognitive function of patients. SRS should be considered initial therapy in patients with a limited number of brain metastases. Citation (S) : SRS should be considered especially in patients with good physical activity status (PS) and small total tumor volume.
The brain was once considered to be an immune privilege organ, which can actively inhibit any immune response. The 2019 NCCN guidelines have recommended immune checkpoint inhibitors (ICIs) as the first-line treatment for some patients with lung cancer, and the application of ICIs in lung cancer with brain metastases is also being explored. Several phase III RCT studies have shown that immunotherapy prolongs the survival of patients with brain metastases.
As a classic treatment for brain metastases from lung cancer, radiotherapy can promote the anti-tumor immune effect by inducing immunogenic cell death, exposing tumor-associated antigens, activating dendritic cells, changing the tumor microenvironment, and enhancing the expression of intercellular adhesion molecule-1 (ICAM-1), Fas and major histocompatibility complex Ⅰ (MHCⅠ) in tumor cells. High-dose fractionated radiotherapy also has immunogenicity, which may open the blood-brain barrier (BBB) and promote the entry of ICI into brain tissue. However, radiotherapy can up-regulate the expression of PD-L1 and inhibit tumor immunity, which can be improved by ICI. In conclusion, intracranial radiotherapy combined with ICIs has feasibility and theoretical basis for the treatment of malignant tumors.
Cadonilimab is a bispecific antibody (BsAb) that can bind to both PD-1 and CTLA-4 with high affinity. It is a novel tumor immunotherapy drug with a quadrivalent structure and a short half-life, and has been shown to have less toxicity than the combination of anti-PD-1 and anti-CTLA-4 antibodies in monkey toxicity studies. These features make it possible that the use of Cadonilimab in cancer subjects may have better efficacy and safety.
In conclusion, the combination of Cadonilimab with radiotherapy has potential advantages and is expected to have the potential to further improve antitumor efficacy. Therefore, the aim of this study is to evaluate the efficacy and safety of Cadonilimab combined with SRS in the treatment of brain metastases from NSCLC, and to provide evidence for future studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cadonilimab combined with SRS | Experimental | Drug: Cadonilimab combined with SRSEligible subjects were treated with stereotactic radiotherapy for brain metastases plus Cadonilimab followed by maintenance therapy with Cadonilimab alone |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 18 years old ≤ 75 years old; Both male and female;
- ECOG 0-1;
- Histologically or cytologically confirmed non-small cell lung cancer;
- Progression with brain metastasis after previous first-line anti-tumor therapy;
- Requirements for brain metastases: ① measurable brain metastases without radiotherapy; ②SRS/FSRT: the maximum tumor volume of brain metastases was less than 10cm3, the single diameter was less than 3cm, and the total volume of brain metastases involved was less than 15 cm3.
Key exclusion criteria (19 listed)
- Subjects who meet any of the following criteria are not eligible to participate in the study:
- Experienced grade 3-4 intracranial toxicity (pituitary or central nervous system toxicity);
- No measurable intracranial metastatic lesions without radiotherapy;
- Meningeal metastasis;
- If receiving chemotherapy or targeted therapy, the washout period should not exceed 3 weeks; if receiving brain metastasis resection, the washout period should not exceed 2 weeks;
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 |
|---|---|---|
| Cadonilimab combined with SRSEligible subjects were treated with stereotactic radiotherapy for brain metastases plus Cadonilimab followed by maintenance therapy with Cadonilimab alone | Drug | Cadonilimab combined with SRS |
Primary outcome
iORR
Time frame: From date of enrollment until the date of first documented intracranial progression, assessed up to 2 years.
Intracranial objective response rate (iORR) was defined as the proportion of patients who achieved a prespecified reduction in tumor volume and maintained the minimum time requirement, including CR and PR cases.
3 secondary outcomes
PFS
Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.
iPFS
Time frame: From date of enrollment until the date of first documented intracranial progression or date of death from any cause, whichever came first, assessed up to 2 years
OS
Time frame: From date of enrollment until the date of death from any cause, whichever came first, assessed up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2024.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cadonilimab combined with SRS in people with Non Small Cell Lung Cancer and Brain Metastases, run by Rongrong Zhou 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 15 inclusion and 19 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: looking for participants now, as of the sponsor's last update on 25 Nov 2024. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rongrong Zhou, MD, PHD (+8613875898127, zhourr@csu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
iORR (time frame: From date of enrollment until the date of first documented intracranial progression, assessed up to 2 years.). 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 25 Nov 2024.