FDA Grants Breakthrough Therapy Designation to DZD9008 for EGFR Exon20Ins-Positive NSCLC


DZD9008 for the treatment of patients with locally advanced or metastatic non–small cell lung cancer harboring with EGFR exon20 insertion mutations is an investigative treatment strategy in a clinical trial.

The FDA has granted breakthrough therapy designation to DZD9008 (sunvozertinib) for the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy, according to a press release by Dizal Pharmaceutical Co. Ltd.1

DZD9008 is a selective, irreversible EGFR inhibitor, which is currently being evaluated for the treatment of both EGFRexon20 insertion mutation-positive NSCLC and HER2-mutated NSCLC. In the open-label, multicenter phase 1/2 study (NCT03974022), 220 patients with EGFRexon20 insertion mutation-positive or HER2-positive NSCLC were treated with DZD9008 at doses of 50 mg to 400 mg once daily.2,3

The primary end point in part A of the study was safety and tolerability, which was assessed to determine the maximum-tolerated dose of the agent and the recommended phase 2 dose (RP2D). The primary end point in part B was objective response rate (ORR), with a secondary end point of plasma DZD9008 concentration.

In a cohort of 97 patients treated at the RP2D of 300 mg once daily, the ORR was 48.4%, and the disease control rate was 90.3%. Further, anti-tumor activity was observed across multiple EGFR exon20 insertion mutation-positive subtypes. Responses were ongoing in some patients beyond 6 months. In terms of safety, the most common grade 3 treatment-emergent adverse events were diarrhea (5.2%) and skin rash (1%).

The study is enrolling patients who are aged 18 years or older with histologically or cytologically confirmed disease, an ECOG performance status of 0-1, a life expectancy of ≥ 12 weeks, measurable disease per RECST v1.1, and adequate organ system function. Patients with brain metastases are permitted if stable, neurologically asymptomatic, and their disease does not require corticosteroids treatment.3

"Lung cancer patients with exon20 insertion mutations need better treatment. Sunvozertinib was specifically designed with high selectivity for inhibiting mutated EGFR, which causes cancers. Available clinical evidence shows that sunvozertinib has the potential to provide the patients with a new and much improved targeted therapy" said Xiaolin Zhang, PhD, chief executive officer, Dizal, in a press release. "We are very pleased with FDA’s decision. Now sunvozertinib has received breakthrough therapy designation from both the US FDA and China CDE, which validates sunvozertinib’s differentiated profile.”

In the US, the study is actively recruiting at sites in California, Colorado, Massachusetts, and New York.


1. FDA grants breakthrough therapy designation for dizal pharmaceutical’s DZD9008 in patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR exon20 insertion. New release. Dizal Pharmaceutical Co. Ltd. January 28, 2022. Accessed January 28, 2022. https://bit.ly/3ulggSf

2. Yang J, Wang M, Mitchel P, et al. Preliminary safety and efficacy results from phase 1 studies of DZD9008 in NSCLC patients with EGFR Exon20 insertion mutations. J Clin Oncol. 2021;39(15):9008-9008. doi: 10.1200/JCO.2021.39.15_suppl.9008

3. Assessing an oral EGFR inhibitor, DZD9008 in patients who have advanced non-small cell lung cancer with EGFR or HER2 mutation (WU-KONG1). Clinicaltrials.gov. Accessed January 28, 2022

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