Trial Title:
Efficacy of Cadonilimab in Non-squamous Non-small Cell Lung Cancer Patients Resistant to EGFR-TKI
NCT ID:
NCT06277674
Condition:
Non-small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Pemetrexed
Conditions: Keywords:
Cadonilimab
Immune checkpoint inhibitors
EGFR-TKI resistance
elderly non-small cell lung cancer patients
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cadonilimab plus Pemetrexed and Anlotinib
Description:
Cadonilimab was administered intravenously at a dose of 10 mg/kg every 3 weeks.
Pemetrexed was administered intravenously at a dose of 500 mg/m² every 3 weeks Anlotinib
was taken at doses of 10mg orally once daily for two weeks on a one-week-off schedule.
Arm group label:
cadonilimab plus pemetrexed and anlotinib
Other name:
ICIs in combination with chemotherapy and antiangiogenic therapy
Summary:
This study was designed to evaluate the efficacy and safety of cadonilimab (anti PD-1 and
CTLA-4 bispecific antibody) in combination with pemetrexed and anlotinib for treatment of
elderly patients with T790M-negative advanced non-squamous non-small cell lung cancer
following resistance to EGFR-TKI.
Detailed description:
This prospective study aims to enroll 20 elderly patients (age≥65 years) with advanced
non-squamous NSCLC with T790M negative after EGFR-TKI resistance. Eligible patients will
be given 4 to 6 cycles of cadonilimab plus pemetrexed and anlotinib, followed by
maintenance treatment with cadonilimab plus anlotinib until disease progression,
intolerable toxicity, withdrawal of consent, death, or other protocol-specified causes,
whichever occurs first. Imaging assessments are scheduled to conduct every 6 weeks for
the first year and then every 12 weeks thereafter. The follow-up of participants who
discontinued treatment for reasons unrelated to disease progression will be continued,
until the initiation of other anti-tumor therapy, disease progression, death, or the end
of the study, whichever occurrs first.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients signed informed consent, willing to accept this regimen, able to adhere to
the medication, and had good compliance.
2. Patients with advanced or metastatic non-small cell lung cancer (stage IIIB, IIIC,
or IV according to the AJCC staging system, 8th edition) diagnosed by histopathology
or cytopathology
3. Histologically or cytologically confirmed, locally advanced or metastatic
nonsquamous non-small-cell lung cancer (stage IIIB, IIIC, or IV according to the
AJCC staging manual, 8th edition) patients with EGFR sensitive mutations (confirmed
by tumour histology, cytology, or cell-free or circulating tumour DNA) progressed
after receiving EGFR tyrosine-kinase inhibitor therapy; confirmed EGFR Thr790Met
negative mutation status after receiving first-generation, second-generation or
third-generation EGFR tyrosine-kinase inhibitor as first-line or second-line
treatment
4. Eastern Cooperative Oncology Group performance status of 0 to 2
5. Presence of at least one measurable lesion
6. An estimated life expectancy of at least 3 months
7. Good organ function was defined as hemoglobin≥90g/L (no blood transfusion within 7
days), absolute neutrophil count ≥1.5×109/L, and platelet count≥100×109/L. Total
bilirubin level≤1.5 times of the upper limit of normal value (ULN), albumin ≥30g/L,
aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times of
upper limit of normal (ULN), in cases with liver metastasis, AST and ALT≤5 times of
ULN; Creatinine ≤1.5 times of ULN; International normalized ratio (INR) or
prothrombin time (PT) ≤1.5 times of ULN, if the participant is receiving
anticoagulant therapy normally, as long as the PT is within the prescribed range of
anticoagulant drugs
Exclusion Criteria:
1. Concomitant driver mutations for which there were known therapies were identified,
including but not limited to ALK rearrangement, ROS1 fusion, or BRAF V600E mutation
2. Previously received systemic anti-tumour therapy (including cytotoxic chemotherapy
and antiangiogenic therapy) except EGFR tyrosine-kinase inhibitors for advanced
NSCLC
3. Previously received immunotherapy (including anti-PD-1, anti-PD-L1, or anti-CTLA-4)
antibodies or agents
4. The presence of an active malignancy within 2 years prior to the first dose was not
allowed. Participants with locally cured tumors, such as basal-cell carcinoma or
squamous-cell carcinoma of the skin, superficial bladder cancer, or carcinoma in
situ of the breast, were not excluded
5. The enrollment of another clinical study was excluded except for observational or
noninterventional studies or interventional studies with a follow-up period
exceeding four weeks after the last dose of the study drug or more than five
half-lives of the study drug
6. Patients received systemic treatment with Chinese patent medicine or Chinese herbal
medicine exhibiting anti-tumor properties or immunomodulatory drugs (such as
thymosin, interferon, interleukin) indicated for anti-tumor purposes within a 2-week
period prior to the initial dosage
7. Participants with an active, known, or suspected autoimmune disease or a history of
autoimmune disease are excluded from the study, except for those with Vitiligo,
alopecia, Graves' disease, psoriasis, or eczema that do not require systemic
treatment for nearly 2 years. Additionally, Participants with asymptomatic
hypothyroidism (due to autoimmune thyroiditis) or stable doses of hormone
replacement therapy and type I diabetes requiring only stable doses of insulin
replacement therapy are also exempted. Furthermore, participants who had childhood
asthma that has completely resolved and no longer require any intervention in
adulthood or whose disease does not recur without an external trigger are eligible
for inclusion
8. Participants who have received systemic treatment with corticosteroids (prednisone
equivalent dose > 10 mg/day) or other immunosuppressive drugs within 14 days prior
to the first dose are excluded
9. Documented history of immunodeficiency
10. Documented history of allogeneic organ transplantation and allogeneic hematopoietic
stem cell transplantation
11. Major surgical procedures (such as laparotomy, thoracotomy, viscerectomy, etc.) or
severe trauma within 28 days prior to the initial administration (intravenous drip
replacement is acceptable); Surgery aimed at improving or reducing the risk of
oncologic complications within 14 days before the first dose; Or incomplete recovery
from any of the aforementioned previous surgeries. Major surgical procedures were
planned (at the investigator's discretion) within 30 days after the initial dose.
Local surgery (e.g., placement of systemic ports, core needle biopsy) was permitted
if performed at least 24 hours prior to initiation of study treatment
12. Patients with a medical history of gastrointestinal perforation, gastrointestinal
fistula, or female genital fistula (such as vesicovaginal fistula, urethrovaginal
fistula, etc.) within the past 6 months prior to the initial drug administration
were eligible for enrollment if the perforation or fistula had been surgically
treated (e.g., excision or repair) and if complete recovery or resolution of the
condition was confirmed by the investigator
13. The presence of interstitial lung disease, whether symptomatic or not, may hinder
the detection or management of suspected drug-related pulmonary toxicity
14. The presence of active pulmonary tuberculosis (TB). Patients suspected to have
active TB underwent examination through chest X-ray and sputum analysis, while being
assessed for clinical signs and symptoms
Gender:
All
Minimum age:
65 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Guangdong Provincial Hospital of Traditional Chinese Medicine
Address:
City:
Guangzhou
Zip:
510120
Country:
China
Status:
Recruiting
Contact:
Last name:
Haibo Zhang, Prof
Phone:
86-020-81887233
Phone ext:
34830
Email:
haibozh@gzucm.edu.cn
Start date:
November 2, 2023
Completion date:
June 2025
Lead sponsor:
Agency:
Guangzhou University of Traditional Chinese Medicine
Agency class:
Other
Collaborator:
Agency:
Akeso Pharmaceuticals, Inc.
Agency class:
Other
Source:
Guangzhou University of Traditional Chinese Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06277674
