Study of DZD9008 Meets Primary End Point of ORR in EGFR Exon20Ins-Positive NSCLC

Topline data presented at ESMO 2022 showed DZD9008 met its primary end point of objective response rate and had a benign safety profile in non–small cell lung cancer with EGFR exon 20 insertion mutations.

DZD9008 (sunvozertinib) in patients with platinum-pretreated non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations whose disease has progressed on/after platinum-based chemotherapy has met its the primary end point of confirmed objective response (ORR) at 59.8%, according to Dizal Pharmaceutical.1

The response rate for patients with baseline brain metastasis was 48.4% and clinical activities were observed across a broad range of EGFR exon 20 insertion mutation subtypes, regardless of mutation positions. Additionally, the safety profile of DZD9008 was benign with mild adverse events (AEs).

DZD9008 is a rationally designed, oral, potent EGFR exon 20 insertion inhibitor, with wild-type EGFR selectivity. Previously, DZD9008 was granted a breakthrough therapy designation by the FDA in January 2022.

"The importance of advancing research on NSCLC with EGFR exon 20 insertions mutation – a complicated and devastating disease – cannot be overstated, as available treatment options provide limited benefit especially to those develop brain metastasis," said Xiaolin Zhang, MD, chief executive officer of Dizal, in the press release. "It is great news to our patients that sunvozertinib is showing such strong antitumor activities with a benign safety profile. This data further strengthens our confidence in [DZD9008] and reinforces its best-in-class position."

Topline data were presented at the 2022 ESMO Congress based on the latest data from the multicenter, single-arm, phase 2 WU-KONG6 study (NCT03974022) conducted in China.

The efficacy set included 97 patients with platinum-pretreated NSCLC harboring EGFR exon20 mutations while the safety set included 277 patients.2

Additional findings showed that DZD9008 demonstrated a favorable safety profile. Among the 277 patients in the safety set, the most common treatment-related AEs were diarrhea and rash. Most of these AEs were grade 1 or 2 and were clinically manageable.

To be enrolled in the study, patients must be 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 RECIST v1.1, and adequate organ system function. Patients with brain metastases are eligible if stable, neurologically asymptomatic, and their disease does not require corticosteroids treatment.

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

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

References:
1. Dizal announces sunvozertinib meets primary endpoint in its first pivotal study in platinum-pretreated NSCLC patients with EGFR exon20ins mutations at 2022 ESMO. News release. Dizal Pharmaceuticals. September 5, 2022. Accessed September 14, 2022. https://prn.to/3RJ0qtr
2. 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 May 31, 2022