Trial Title:
Envafolimab Immunotherapy After ctDNA EGFR Clearance by Treatment With Almonertinib in EGFR-Mutant, PD-LI Positive NSCLC
NCT ID:
NCT05534113
Condition:
Non-small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Conditions: Keywords:
EGFR
ctDNA
PD-L1
NSCLC
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Almonertinib Envafolimab
Description:
Subjects will receive Almonertinib treatment for 6-8 weeks after enrollment, and receive
ctDNA detection and radiography assessment again.
If the EGFR mutation is positive, according to the patient's condition and clinical
actual situation, subjects will receive combination therapy scheme, follow-up once every
6 weeks. The treatment will continue until the disease progress assessed by radiography.
If the EGFR mutation turns negative and stable radiographically deep response, stop
Almonertinib treatment and receive the relevant assessment before immunotherapy and
receive Envafolimab treatment，and follow-up once every 6 weeks. The treatment of
Envafolimab will continue until the EGFR mutation is positive again or disease progress
assessed by radiography.
Arm group label:
sequential Envafolimab therapy after Almonertinib treatment
Summary:
This is a prospective, single-arm, open-label, interventional clinical study, aimed at
exploring the efficacy and safety of sequential Envafolimab immunotherapy after patients
with ctDNA EGFR mutation clearance and achieved stable radiographically deep esponse
after first line treatment with Almonertinib in EGFR-Mutant, PD-LI positive
non-small-cell lung cancer.
Detailed description:
The study includes a screening period (not more than 28 days after the subject signs
informed consent to before the first medication), treatment period (including
Almonertinib treatment in 6-8 weeks after enrollment\ctDNA testing and radiographically
imaging assessment\ctDNA guiding sequential Envafolimab immunotherapy) and follow-up
period (including survival and safety) .
Eligible subjects receive 110 mg of Almonertinib once a day for 6-8 consecutive weeks of
treatment，and receive ctDNA testing and radiographically imaging assessment again.
According to test results, there are two types:
1. EGFR mutation is positive, subjects subsequent treament is up to the investigator
(continue to receive 110 mg of Almonertinib once a day or combination therapy
regimen), follow up every 6 weeks.
2. EGFR mutation is negative and achieve stable radiographically deep response after
6-8 weeks treatment with Almonertinib, subjects will stop Almonertinib treatment，and
receive sequential Envafolimab immunotherapy (ctDNA dynamic monitoring guided
treatment，every 6 weeks test ctDNA once, if it is negative, subjects continue to
receive Envafolimab immunotherapy until ctDNA EGFR turns positive; if ctDNA EGFR is
positive, subjects stop Envafolimab immunotherapy and receive Almonertinib 110 mg
once a day again until ctDNA EGFR turns negative).
The treatment will continue until disease progression assessed by the investigator
according to RECIST 1.1 criteria, or withdrawal or termination criteria are reached.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Over 18 years old (including 18 years old) .
- The Eastern Cooperative Oncology Group (ECOG) physical status score is 0 to 1, and
it has not deteriorated in the previous 2 weeks, and the minimum expected survival
is 12 weeks.
- Unresectable advanced or metastatic non-squamous cell non-small cell lung cancer.
- Blood samples were confirmed to contain EGFR-sensitive mutations by ctDNA
testing(including exon 19 deletion or L858R, both alone or coexist with other EGFR
mutations.Patients with EGFR20 exon insertion mutations could not be enrolled).
- No systematic antitumor treatment before enrollment.
- PD-L1 expression is positive, defined as TPS (tumor proportion score) ≥10%.
- The patient has at least one tumor lesion that can be accurately measured at
baseline, and the longest diameter at baseline is ≥10 mm (if it is a lymph node, the
short diameter is required to be ≥15 mm). The selected measurement method is
suitable for accurate repeat measurement, which can be computed tomography (CT) or
magnetic resonance scan (MRI). If there is only one measurable lesion, it can be
accepted as the target lesion, and a baseline assessment of the tumor lesion should
be performed at least 14 days after the diagnostic biopsy.
- Women of childbearing age should take appropriate contraceptive measures from
screening to 3 months after stopping the study treatment and should not breastfeed.
Before starting the administration, the pregnancy test is negative, or meeting one
of the following criteria proves that there is no risk of pregnancy:
1. Postmenopausal is defined as age greater than 50 years，and amenorrhea for at
least 12 months after stopping all exogenous hormone replacement therapy.
2. For women younger than 50 years old, if the amenorrhea is 12 months or more
after stopping all exogenous hormone treatments, and the luteinizing hormone
(LH) and follicle stimulating hormone (FSH) levels are within the laboratory
postmenopausal reference value range, also It can be considered postmenopausal.
3. Have received irreversible sterilization, including hysterectomy, bilateral
ovariectomy or bilateral fallopian tube resection, except for bilateral
fallopian tube ligation.
- Male subjects should use barrier contraception (ie, condoms) from screening to 3
months after the study treatment is stopped.
- The subjects themselves participated voluntarily and signed a written informed
consent form.
Exclusion Criteria:
Subjects who meet any of the following criteria cannot be included in this study:
- Have received any of the following treatments:
1. Previously received antitumor treatment for lung cancer in the past;
2. Previously received Chinese patent medicine with anti-tumor effect. If Chinese
patent medicine with anti-tumor effect has been received for no more than 7
days, and the medicine has been stopped for 2 weeks or more before the drug
treatment of this study, it can be included in the group.
- Patients who had received open surgery on other parts except lungs within 14 days
before using the study drug ≤ 14 days.
- Refractory nausea, vomiting or chronic gastrointestinal diseases, inability to
swallow the study drug or having undergone extensive intestinal resection may affect
the full absorption of Almonertinib.
- Patients with other malignant tumors in recent 5 years (excluding completely
resected basal cell carcinoma, bladder cancer in situ and cervical carcinoma in
situ).
- Have a history of interstitial lung disease, a history of drug-induced interstitial
lung disease, a history of interstitial pneumonia requiring steroid treatment, or
any evidence of clinically active interstitial lung disease.
- As judged by the investigator, there are any serious or poorly controlled systemic
disease, such as poorly controlled hypertension, active bleeding or active infection
(including active fungal, bacterial and / or viral infections requiring systemic
treatment or full-body anti infective drugs used within one week before the first
administration).
- At the beginning of the study treatment, there were unresponsive residual toxicity
from previous treatment that was greater than CTCAE grade 3, except for hair loss.
- Meet any of the following cardiac examination results:
1. The average value of QT interval (QTcF) corrected by Fridericia's formula
obtained from 3 ECG examinations at rest> 470 msec;
2. Resting ECG suggests that there are various clinically significant rhythms,
conduction or ECG morphological abnormalities that are judged by the
investigator (such as complete left bundle branch block, 3 degree
atrioventricular block, 2 degree atrium Ventricular block and PR interval> 250
msec, etc.);
3. There are any factors that increase the risk of QTc prolongation or arrhythmia
events, such as heart failure, hypokalemia, congenital long QT syndrome, family
history of long QT syndrome, or unexplained sudden death or prolonged QT of
immediate family members under 40 Any concomitant drugs in the interval;
4. Left ventricular ejection fraction (LVEF) <50%.
- Insufficient bone marrow reserve or organ function, reaching any one of the
following laboratory limits (no corrective treatment within 1 week before laboratory
examination of blood draw):
1. Absolute neutrophil count <1.5×109 / L; Platelet count <100×109 / L; Hemoglobin
<90 g/L (<9 g/dL);
2. Liver function: alanine aminotransferase > 3 times the upper limit of normal
(ULN); Aspartate aminotransferase > 3uln; Total bilirubin > 1.5uln; Serum
albumin (ALB) < 28 g / L.
3. Renal function: creatinine > 1.5 ULN or creatinine clearance < 50ml / min
(calculated by Cockcroft Gault formula). Only when creatinine ≥ 1.5 ULN, it is
necessary to confirm creatinine clearance.
- Female subjects who are pregnant, lactating, or planning to become pregnant during
the study period.
- Have a history of hypersensitivity to any active or inactive ingredients of
almonertinib or to drugs with similar chemical structure to almonertinib or the same
class of almonertinib.
- Any serious or uncontrolled eye disease (especially severe dry eye syndrome, dry
keratoconjunctivitis, severe exposure keratitis or other diseases that may increase
epithelial damage) may increase the safety of the patient by the doctor's judgment
Sexual risk; or those with eye abnormalities that require surgery or are expected to
require surgical treatment during the study period.
- Use / eat drugs or foods that are known to have strong CYP3A4 inhibition effect
within 2 weeks (including but not limited to azanavir, clarithromycin, indinavir,
itraconazole, ketoconazole, nefazodone, nefenavir, ritonavir, saquinavir,
telithromycin, acephaeomycin, voriconazole and grapefruit or grapefruit juice).
- Use drugs known to have strong CYP3A4 inducing effect (including but not limited to
carbamazepine, phenobarbital, phenytoin, rifampin, rifampicin and Hypericum
perforatum) within 2 weeks.
- Use drugs (including but not limited to dihydroergotamine, ergotamine, pimozide,
astemizole, cisapride and terfenadine) as CYP3A4 substrates (with narrow therapeutic
index) within 2 weeks.
- Have used strong P-gp inhibitors within 2 weeks (including but not limited to
verapamil, cyclosporine A and dexverapamil)
- Patients with previous autoimmune diseases or undergoing immunomodulatory treatment.
- Subjects who may have poor compliance with the study procedures and requirements at
the judgment of the investigator, such as those who have a clear history of
neurological or mental disorders (including epilepsy or dementia) in the past, and
those who currently suffer from mental disorders.
- Patients who need long-term systemic corticosteroids. Patients with COPD and asthma
requiring intermittent use of bronchodilators, inhaled corticosteroids, or local
injection of corticosteroids can be enrolled.
- Symptomatic central nervous system metastasis. Patients with asymptomatic brain
metastases or brain metastases whose symptoms are stable after treatment can
participate in this study as long as they meet all the following criteria: there are
measurable lesions outside the central nervous system; No midbrain, pons,
cerebellum, meninges, medulla oblongata or spinal cord metastasis; Maintain clinical
stability for at least 2 weeks; Hormone therapy was stopped 3 days before the first
dose of study drug.
- Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 / 2
antibody positive).
- Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number
detected is greater than the upper limit of the normal value of the laboratory of
the research center); Note: hepatitis B subjects meeting the following criteria can
also be included in the group:
1. HBV viral load before the first administration was < 1000 copies / ml (200 IU /
ml), and the subject should receive anti HBV treatment during the whole study
chemotherapy drug treatment period to avoid virus reactivation;
2. For subjects with anti HBC (+), HBsAg (-), anti HBS (-) and HBV viral load (-),
preventive anti HBV treatment is not required, but viral reactivation needs to
be closely monitored..
- Active HCV infected subjects (HCV antibody is positive and HCV-RNA level is higher
than the lower limit of detection).
- Have received live vaccine within 30 days before the first administration (cycle 1,
day 1); Note: it is allowed to receive inactivated virus vaccine for injection
against seasonal influenza within 30 days before the first administration; subjects
have received live attenuated influenza vaccine for intranasal administration is not
allowed.
- Investigator judges that there are any patients with conditions that endanger the
safety of the patient or interfere with the evaluation of the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
December 1, 2022
Completion date:
June 1, 2025
Lead sponsor:
Agency:
The First Affiliated Hospital with Nanjing Medical University
Agency class:
Other
Source:
The First Affiliated Hospital with Nanjing Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05534113
