Zipalertinib With Carboplatin and Pemetrexed for the Treatment of Resectable, Stage II-IIIB, Non-Small Cell Lung Cancer

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.