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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
40
The dosage and protocol of the drug were carried out according to the description.
The dosage and protocol of the drug were carried out according to the description.
The dosage and protocol of the drug were carried out according to the description.
Affiliated Hospital of Jiangnan University
Wuxi, Jiangsu, China
RECRUITINGObjective response rate
Total response and partial response ratio
Time frame: 8 weeks
Progression-free survival
Time from randomization to any disease progression and/or death, defined according to strict RECIST (Response Evaluation Criteria in Solid Tumors) v1.1. Lesion will be assessed in comparison to baseline measurements.
Time frame: 1 year
Overall survival
Randomize time to date of death or last known alive date calculation.
Time frame: 72 weeks
Disease control rate
The proportion of patients with a best response grade of complete response, partial response, or stable disease that has shrunk or stabilized for a period of time.
Time frame: an average of 1 year
Objective response rate
Assessed according to disease progression as defined by RECIST (Response Evaluation Criteria in Solid Tumors) v1.1
Time frame: 72 weeks
Changes in tumor volume shrinking
Change in tumor volume reduction from randomization to 6 months
Time frame: 6 months
Tolerability and Safety
Assessed based on the number of treatment reductions, delays and withdrawals, including the incidence and nature of dose-limiting toxicities.
Time frame: an average of 1 year
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.