Clinical trial NCT05573373: Pamiparib (BGB-290) Was Used in EGFR-TkIs Resistant Non-small Cell Lung Cancer
Official title: Double Arm Single Center Clinical Trial of Pamiparib (BGB-290) for EGFR TKIs Resistant Non-small Cell Lung Cance
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
EGF-R Positive Non-Small Cell Lung Cancer
Lead sponsor: Affiliated Hospital of Jiangnan University
Sponsor class: OTHER
First posted: 2022-10-10
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Primary outcomes:
measure: Objective response rate
timeFrame: 8 weeks
Secondary outcomes:
measure: Progression-free survival
timeFrame: 1 year
measure: Overall survival
timeFrame: 72 weeks
measure: Disease control rate
timeFrame: an average of 1 year
measure: Objective response rate
timeFrame: 72 weeks
measure: Changes in tumor volume shrinking
timeFrame: 6 months
measure: Tolerability and Safety
timeFrame: an average of 1 year
Other outcomes:
Locations:
city: Wuxi
country: China
facility: Affiliated Hospital of Jiangnan University
state: Jiangsu
Study officials:
affiliation: Affiliated Hospital of Jiangnan University
name: liu quan, doctor
role: PRINCIPAL_INVESTIGATOR
References: