Trial Title:
Pamiparib (BGB-290) Was Used in EGFR-TkIs Resistant Non-small Cell Lung Cancer
NCT ID:
NCT05573373
Condition:
Carcinoma, Non-Small-Cell Lung
EGF-R Positive Non-Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Poly(ADP-ribose) Polymerase Inhibitors
Antineoplastic Agents
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Single (Participant)
Intervention:
Intervention type:
Drug
Intervention name:
Parimparib
Description:
The dosage and protocol of the drug were carried out according to the description.
Arm group label:
Pamilarib in combination with Chemotherapy Drugs
Arm group label:
Pamiparib in combination with Targeted Therapy Drugs
Other name:
BGB-290
Other name:
Poly (ADP-ribose) polymerase (PARP) inhibitor
Intervention type:
Drug
Intervention name:
Chemotherapy drug
Description:
The dosage and protocol of the drug were carried out according to the description.
Arm group label:
Pamilarib in combination with Chemotherapy Drugs
Other name:
Chemotherapy Drug, Cancer
Intervention type:
Drug
Intervention name:
Targeted Therapy Agent
Description:
The dosage and protocol of the drug were carried out according to the description.
Arm group label:
Pamiparib in combination with Targeted Therapy Drugs
Other name:
Targeted drug
Summary:
The purpose of this study was to investigate the efficacy and safety of pamiparib in
patients with EGFR-TKIs-resistant NSCLC, using a single-center, dual-arm, open-label
design.
Detailed description:
Lung cancer is the second most common cancer type worldwide and remains the leading cause
of cancer death worldwide. Non-small cell lung cancer accounts for 80% of the total
number of lung cancers, 15-55% of NSCLC have EGFR mutations, of which about 50% of
Asians, targeted drugs - epidermal growth factor receptor-tyrosine kinase inhibitors
(EGFR-TKIs) ) showed good clinical benefit. However, patients with EGFR-mutant lung
cancer experience disease progression within about a year of treatment with EGFR-TKIs,
and acquired resistance develops and limits the long-term efficacy of these EGFR-TKIs.
About 50% of EGFR-TKIs acquired resistance mutations by the mechanism of T790 mutation.
Third-generation EGFR-TKIs can be used to overcome drug resistance against T790 mutation.
Unfortunately, acquired resistance to third-generation EGFR-TKIs will eventually emerge,
and when third-generation EGFR-TKIs acquire resistance, effective treatment options are
still being explored. PARP (poly(ADP-ribose) polymerase) inhibitors represent a new class
of anticancer therapy. They exploit synthetic lethality and induce cell death by
exploiting defects in DNA repair, poly(ADP-ribose) polymerase-1 (PARP1) and
poly(ADP-ribose) polymerase-2 (PARP2) are PARP enzymes Members of the family that play
key roles in the DNA damage response (DDR) by acting as DNA damage sensors and signal
transducers. PARP inhibitors can be used in combination with conventional NSCLC treatment
regimens or as monotherapy. In clinical applications, PARP inhibitors have demonstrated
sustained antitumor responses as single agents in BRCA1- or BRCA2-mutated patients.
Studies have shown that the single-drug toxicity of PARP inhibitors is much lower than
that of platinum drugs, and experimental results in NSCLC cell lines have shown that PARP
inhibitors have single-drug activity in NSCLC. The characteristics of the domestic PARP
inhibitor, Pamiparib, reflect its advantages over other PARP inhibitors: 1)low drug
resistance, 2)high selectivity, 3)high capture of PARP-DNA complexes, 4)high membrane
permeability, 5)Dual pathway metabolism, 6)Blood-brain barrier permeability. Multiple
clinical data show that Pamiparib as a single agent has favorable safety and antitumor
activity in advanced recurrent solid tumors.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female patients: ≥18 years old
2. Histologically or cytologically confirmed non-small cell lung cancer, and the
disease has progressed after first-generation and/or second-generation TKIs
treatment with first-line therapy and no T790 mutation, or after third-generation
EGFR-TKI treatment After the disease progresses, the guidelines do not recommend a
standard protocol.
3. No other concurrent cancer.
4. At least one previously unirradiated lesion that can be accurately measured at
baseline with longest diameter ≥ 10 mm (must have a short lymph node excluding axis
≥ 15 mm) according to RECIST criteria with computed tomography (CT), magnetic
resonance imaging (MRI) or clinical examination for accurate repeated measures. Or
an unevaluable lesion, including but not limited to pleural and ascites, bone
metastasis, etc.
5. ECOG physical condition score: 0-3 points.
6. Expected survival period ≥ 3 months.
7. The function of major organs is good, that is, the relevant inspection indicators
within 14 days before randomization meet the following requirements: a) Routine
blood test:i. Hemoglobin ≥ 90 g/L (no blood transfusion within 14 days); ii.
Neutrophil count > 1.5×109/L; iii. Platelet count ≥ 90×109/L; b) Biochemical
examination: i. Total bilirubin ≤ 1.5×ULN (upper limit of normal); ii. Blood alanine
aminotransferase (ALT) or blood aspartate aminotransferase (AST) ≤ 2.5×ULN; if liver
metastasis, ALT or AST ≤ 5×ULN; iii. Endogenous creatinine clearance ≥ 60 ml/min
(Cockcroft-Gault formula); c) Cardiac Doppler ultrasound assessment: Left
ventricular ejection fraction (LVEF) ≥ 50%.
8. Sign the informed consent.
9. The patient is willing and able to comply with the protocol during the study,
including receiving treatment and scheduled visits and examinations, including
follow-up.
Exclusion Criteria:
1. Participated in clinical trials of other drugs within four weeks.
2. Histologically or cytologically confirmed small cell, large cell neuroendocrine or
carcinoid.
3. There are clinical symptoms or diseases of the heart that cannot be well controlled,
such as: NYHA class 2 or higher heart failure, unstable angina pectoris, myocardial
infarction within 1 year, clinically significant supraventricular or ventricular
arrhythmia requiring treatment or intervention of patients.
4. For female subjects: should be surgically sterilized, postmenopausal patients, or
agree to use a medically approved contraceptive during the study treatment period
and within 6 months after the end of the study treatment period; Serum or urine
pregnancy test must be negative within 7 days and must be non-nursing. Male
subjects: Patients who should be surgically sterilized, or who agree to use a
medically-approved contraceptive method during the study treatment period and within
6 months after the end of the study treatment period.
5. The patient has active pulmonary tuberculosis, bacterial or fungal infection (≥
grade 2 of NCI-CTC, 3rd edition); HIV infection, HBV infection, HCV infection.
6. Those who have a history of psychotropic substance abuse and cannot quit or have
mental disorders.
7. The subject has any active autoimmune disease or has a history of autoimmune disease
(such as the following, but not limited to: interstitial pneumonia, uveitis,
enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, thyroid Reduced
function; subjects with vitiligo or complete remission of asthma in childhood
without any intervention in adulthood can be included; subjects with asthma
requiring bronchodilator medical intervention are not included).
8. According to the judgment of the investigator, there are concomitant diseases that
seriously endanger the patient's safety or affect the patient's completion of the
study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Affiliated Hospital of Jiangnan University
Address:
City:
Wuxi
Zip:
214000
Country:
China
Status:
Recruiting
Contact:
Last name:
liu quan, doctor
Phone:
15995299079
Email:
quanliu@jiangnan.edu.cn; quanliu.lq@outlook.com
Investigator:
Last name:
liu quan, doctor
Email:
Principal Investigator
Start date:
December 20, 2022
Completion date:
December 30, 2025
Lead sponsor:
Agency:
Affiliated Hospital of Jiangnan University
Agency class:
Other
Source:
Affiliated Hospital of Jiangnan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05573373
