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Study to Evaluate the Safety and Efficacy of Serplulimab Plus Bevacizumab and Chemotherapy in NSCLC Patients With Brain Metastases (SUPER BRAIN)

Primary Purpose

Non-small Cell Lung Cancer Stage II, Bevacizumab, Immunotherapy

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Serplulimab combined with bevacizumab and first-line chemotherapy
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer Stage II focused on measuring bevacizumab, Serplulimab, efficacy, non-small cell lung cancer, brain metastases

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Subjects with stage IV non-squamous non-small cell lung cancer (nsqNSCLC) with brain metastases confirmed by histopathology or cytology; The patient should provide a gene test report within 3 months, and the gene report showed negative driver gene, that is, no EFGR sensitive gene mutation, no ALK or ROS1 gene fusion; MRI confirmed brain parenchymal metastasis with ≥3 brain lesions; Or have 1-2 brain lesions but not suitable for local treatment or refuse local treatment patients. There must be at least 1 measurable lesion with a diameter ≥5mm in the brain; Patients with local meningeal metastases were allowed, but patients with extensive meningeal metastases were not included; For asymptomatic BMS or BMS whose intracranial hypertension symptoms were controlled after dehydration treatment, medication could be continued at the time of enrollment or during the study period to keep symptoms stable; There was at least one measurable target lesion as assessed by RECIST v1.1 within 4 weeks prior to initial medication; The patient agrees to provide the genetic test results within 3 months; if not, the patient shall provide the tumor tissue that meets the requirements for genetic test; ECOG PS score is 0-1; Good functioning of vital organs Exclusion Criteria: A known history of severe allergy to any monoclonal antibody (NCI-CTCAE 5.0 grade greater than 3); Or known hypersensitivity to carboplatin/pemetrexed components; Any active infection requiring systemic anti-infective therapy occurs within 14 days prior to initial administration; A history of myocardial infarction and poorly controlled arrhythmias (including QTc interval ≥450 ms in men and 470 ms in women) within 6 months prior to initial administration (QTc interval calculated by Fridericia formula); Or left ventricular ejection fraction according to NYHA standard for Grade III-IV cardiac insufficiency or color Doppler ultrasound < 50%; The subjects had ≥ grade 2 CTCAE peripheral neuropathy; The subject has uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionic calcium or calcium > 12 mg/dL or corrected serum calcium > ULN); Subjects with prior or screening history of interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, and severe impairment of lung function, which the investigators judged might interfere with the detection and management of suspected drug-related pulmonary toxicity; Hepatitis B patients [hepatitis B surface antigen (HBsAg) positive and detection of HBV-DNA suggests viral replication]; Or hepatitis C patients [hepatitis C virus (HCV) antibody positive and HCV-RNA test indicates viral replication]; Or syphilis screening positive (specific antibody test positive, non-specific antibody test negative and combined with clinical diagnosis confirmed as non-active infection); Or a known human immunodeficiency virus (HIV) positive history or HIV screening positive; Subjects have known active or suspected autoimmune diseases. Subjects in stable state who did not require systemic immunosuppressive therapy were admitted; Other active malignancies within 5 years or at the same time. Localized tumors that have been cured for more than 5 years, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder carcinoma, prostate carcinoma in situ, cervical carcinoma in situ and breast carcinoma in situ, can be included in the group. Those who received live or attenuated vaccines within 28 days prior to the first dose or have plans to receive such vaccines during the study period; But inactivated virus vaccines for seasonal influenza are allowed.

Sites / Locations

  • Likun Chen

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Serplulimab combined with bevacizumab and first-line chemotherapy

Arm Description

Serplulimab combined with bevacizumab and first-line chemotherapy

Outcomes

Primary Outcome Measures

iPFS
The time from receipt of study treatment to intracranial tumor PD or to death due to any cause,whichever came first,

Secondary Outcome Measures

PFS
The time from receipt of study treatment to PD or to death due to any cause,,whichever came first,
OS
The time interval between enrollment and death from any cause
iORR
The number and percentage of objective response (PR+CR) of intracranial tumor at each time point after treatment

Full Information

First Posted
March 13, 2023
Last Updated
April 10, 2023
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT05807893
Brief Title
Study to Evaluate the Safety and Efficacy of Serplulimab Plus Bevacizumab and Chemotherapy in NSCLC Patients With Brain Metastases
Acronym
SUPER BRAIN
Official Title
A Multicenter, Single-arm, Open Study to Evaluate the Safety and Efficacy of Serplulimab in Combination With Bevacizumab and First-line Chemotherapy in Driver Negative Non-squamous NSCLC Patients With Brain Metastases
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 14, 2023 (Anticipated)
Primary Completion Date
March 22, 2025 (Anticipated)
Study Completion Date
March 22, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A multicenter, single-arm, open study to evaluate the safety and efficacy of Serplulimab in combination with bevacizumab and first-line chemotherapy in driver negative non-squamous NSCLC patients with brain metastases
Detailed Description
This is a multicenter, single-arm, open study. Thirty patients with stage IV nsqNSCLC with BMs confirmed by histopathology or cytology and reported negative driver genes within three months were enrolled. To evaluate the safety, tolerability and efficacy of Serplulimab combined with bevacizumab and first-line chemotherapy in driver negative nsqNSCLC subjects with brain metastases. Qualified subjects were selected and entered into the study in sequence. The trial was divided into combination chemotherapy period (C1-C4/C6) and maintenance treatment period (C5/C7-C32). In combination chemotherapy period, all subjects were treated with Serplulimab combined with bevacizumab and chemotherapy agents after entering the study, and in maintenance treatment period, Serplulimab combined with bevacizumab and pemetrexed. The efficacy was evaluated every 3 weeks (Q3W), every 2 cycles in combination chemotherapy and every 3 cycles in maintenance treatment. All subjects received treatment until subjects withdrew their informed consent, disease progression, intolerable toxicity, investigator judgment that medication must be discontinued, loss of follow-up, death, or 2 years of use of Serplulimab, whichever occurred first; At the end of treatment, patients were followed up for survival until death.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer Stage II, Bevacizumab, Immunotherapy, Brain Metastases
Keywords
bevacizumab, Serplulimab, efficacy, non-small cell lung cancer, brain metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Serplulimab combined with bevacizumab and first-line chemotherapy
Arm Type
Experimental
Arm Description
Serplulimab combined with bevacizumab and first-line chemotherapy
Intervention Type
Drug
Intervention Name(s)
Serplulimab combined with bevacizumab and first-line chemotherapy
Intervention Description
Serplulimab combined with bevacizumab and first-line chemotherapy
Primary Outcome Measure Information:
Title
iPFS
Description
The time from receipt of study treatment to intracranial tumor PD or to death due to any cause,whichever came first,
Time Frame
The time from receipt of study treatment to intracranial tumor PD or to death due to any cause,whichever came first, assessed up to 60 months
Secondary Outcome Measure Information:
Title
PFS
Description
The time from receipt of study treatment to PD or to death due to any cause,,whichever came first,
Time Frame
The time from receipt of study treatment to PD or to death due to any cause,whichever came first, assessed up to 60 months.
Title
OS
Description
The time interval between enrollment and death from any cause
Time Frame
The time interval between enrollment and death from any cause,,whichever came first, assessed up to 60 months.
Title
iORR
Description
The number and percentage of objective response (PR+CR) of intracranial tumor at each time point after treatment
Time Frame
The number and percentage of objective response (PR+CR) of intracranial tumor at each time point after treatment, through study completion, an average of 2 year.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Subjects with stage IV non-squamous non-small cell lung cancer (nsqNSCLC) with brain metastases confirmed by histopathology or cytology; The patient should provide a gene test report within 3 months, and the gene report showed negative driver gene, that is, no EFGR sensitive gene mutation, no ALK or ROS1 gene fusion; MRI confirmed brain parenchymal metastasis with ≥3 brain lesions; Or have 1-2 brain lesions but not suitable for local treatment or refuse local treatment patients. There must be at least 1 measurable lesion with a diameter ≥5mm in the brain; Patients with local meningeal metastases were allowed, but patients with extensive meningeal metastases were not included; For asymptomatic BMS or BMS whose intracranial hypertension symptoms were controlled after dehydration treatment, medication could be continued at the time of enrollment or during the study period to keep symptoms stable; There was at least one measurable target lesion as assessed by RECIST v1.1 within 4 weeks prior to initial medication; The patient agrees to provide the genetic test results within 3 months; if not, the patient shall provide the tumor tissue that meets the requirements for genetic test; ECOG PS score is 0-1; Good functioning of vital organs Exclusion Criteria: A known history of severe allergy to any monoclonal antibody (NCI-CTCAE 5.0 grade greater than 3); Or known hypersensitivity to carboplatin/pemetrexed components; Any active infection requiring systemic anti-infective therapy occurs within 14 days prior to initial administration; A history of myocardial infarction and poorly controlled arrhythmias (including QTc interval ≥450 ms in men and 470 ms in women) within 6 months prior to initial administration (QTc interval calculated by Fridericia formula); Or left ventricular ejection fraction according to NYHA standard for Grade III-IV cardiac insufficiency or color Doppler ultrasound < 50%; The subjects had ≥ grade 2 CTCAE peripheral neuropathy; The subject has uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionic calcium or calcium > 12 mg/dL or corrected serum calcium > ULN); Subjects with prior or screening history of interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, and severe impairment of lung function, which the investigators judged might interfere with the detection and management of suspected drug-related pulmonary toxicity; Hepatitis B patients [hepatitis B surface antigen (HBsAg) positive and detection of HBV-DNA suggests viral replication]; Or hepatitis C patients [hepatitis C virus (HCV) antibody positive and HCV-RNA test indicates viral replication]; Or syphilis screening positive (specific antibody test positive, non-specific antibody test negative and combined with clinical diagnosis confirmed as non-active infection); Or a known human immunodeficiency virus (HIV) positive history or HIV screening positive; Subjects have known active or suspected autoimmune diseases. Subjects in stable state who did not require systemic immunosuppressive therapy were admitted; Other active malignancies within 5 years or at the same time. Localized tumors that have been cured for more than 5 years, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder carcinoma, prostate carcinoma in situ, cervical carcinoma in situ and breast carcinoma in situ, can be included in the group. Those who received live or attenuated vaccines within 28 days prior to the first dose or have plans to receive such vaccines during the study period; But inactivated virus vaccines for seasonal influenza are allowed.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Likun Chen
Phone
13798019964
Email
chenlk@sysucc.org.cn
Facility Information:
Facility Name
Likun Chen
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Likun Chen
Phone
13798019964
Email
chenlk@sysucc.org.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study to Evaluate the Safety and Efficacy of Serplulimab Plus Bevacizumab and Chemotherapy in NSCLC Patients With Brain Metastases

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