Zipalertinib With Carboplatin and Pemetrexed for the Treatment of Resectable, Stage II-IIIB, Non-Small Cell Lung Cancer
brief summary
This phase II trial tests how well zipalertinib with carboplatin and pemetrexed works in treating stage II-IIIB non small cell lung cancer. that can be removed by surgery (resectable). Zipalertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make DNA and may kill tumor cells. Giving zipalertinib with carboplatin and pemetrexed may kill more tumor cells in patients with resectable, stage II-IIIB non-small cell lung cancer.
detailed description
PRIMARY OBJECTIVE:
I. To evaluate the major pathologic response (MPR) rate of neoadjuvant zipalertinib plus carboplatin and pemetrexed chemotherapy at time of surgery in patients with resectable EGFR Ex20ins-mutated or uncommon/compound EGFR-mutated non-squamous non small cell lung cancer (NSCLC).
SECONDARY OBJECTIVES:
I. To evaluate the efficacy of zipalertinib plus chemotherapy as measured by overall response rate (ORR), pathologic complete response (pCR), event-free survival (EFS), and nodal downstaging.
II. To evaluate the safety and tolerability of zipalertinib plus chemotherapy.
EXPLORATORY OBJECTIVE:
I. To assess potential prognostic and predictive biomarkers using circulating tumor deoxyribonucleic acid (DNA) dynamics through next-generation sequencing using the Tempus platform.
OUTLINE:
NEOADJUVANT: Patients receive zipalertinib orally (PO) twice daily (BID) on days 1-21, and carboplatin intravenously (IV), over 15-60 minutes, and pemetrexed IV, over 10 minutes, on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Within 30 days patients undergo standard of care resection surgery.
ADJUVANT: Between 4 and 12 weeks after surgery patients receive zipalertinib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo positron emission tomography (PET)/computed tomography (CT) scan and/or magnetic resonance imaging (MRI) during screening and CT scan and blood and urine sample collection throughout the study.
After completion of study treatment, patients are followed up at 30 days and every 12 weeks for up to 1 year or until cancer progression or initiation of a new cancer therapy, whichever occurs first.
official title
Phase 2 Trial of Zipalertinib in Patients With Resectable Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion or Uncommon/Compound Mutations