Single-Agent Sunvozertinib Elicits Responses in Advanced NSCLC Harboring EGFR Exon 20 Insertion Mutations

Sunvozertinib (DZD9008) monotherapy produced meaningful responses in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations who received prior treatment with platinum-based chemotherapy, according to pooled data from the phase 1 WU-KONG1 (NCT03974022) and WU-KONG2 (CTR20192097) trials, plus the phase 2 WU-KONG6 trial (CTR20211009), presented at the 2022 World Conference on Lung Cancer.¹

In pooled results from the studies, the overall response rate (ORR) for all patients treated with various doses of sunvozertinib (n = 119) was 47.9%, with all responders achieving a partial response (PR). Notably, 35.3% of patients had a confirmed PR, and 8.4% of patients had a PR pending confirmation. The stable disease (SD) and progressive disease (PD) rates were 43.7% and 12.6%, respectively.

The best ORR for patients treated with 300 mg of sunvozertinib (n = 84) was 52.4%, with a 38.1% confirmed PR rate, a 9.5% PR rate pending confirmation, a 41.7% SD rate, and a 10.7% PD rate.

“About 30 [EGFR] exon 20 insertion subtypes were confirmed in the study. Antitumor activity [was] observed regardless of mutation positions,” lead study author James Chih-Hsin Yang, MD, PhD, a professor and the director of the Graduate Institute of Oncology at the National Taiwan University, and coauthors, wrote in the poster presentation of the data.

Sunvozertinib is a rationally designed, oral EGFR exon 20 insertion inhibitor with EGFR wild-type selectivity. Prior clinical studies showed significant antitumor activity with sunvozertinib. In January 2022, the FDA granted a breakthrough therapy designation to sunvozertinib for the treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.²

The WU-KONG1 and WU-KONG2 trials featured dose-escalation and -expansion portions, evaluating sunvozertinib in platinum-pretreated patients with EGFR exon 20 insertion–mutated locally advanced or metastatic NSCLC. The ongoing WU-KONG6 trial is further investigating sunvozertinib at 300 mg given once daily.

WU-KONG1 and WU-KONG2 examined sunvozertinib administered once daily at doses of 50 mg, 100 mg, 200 mg, 300 mg, and 400 mg in the dose-escalation phase. Doses of 200 mg, 300 mg, and 400 mg were evaluated in the dose-expansion phase. The trials aimed to analyze the relationship between prior treatment with the safety and efficacy of sunvozertinib.

Among the 119 patients in the pooled efficacy analysis, the median age was 58 years (range, 29-85), 61.3% of patients were female, 89.1% of patients were Asian, and 10.9% of patients were White. Sixty-three percent of patients had an ECOG performance status of 1 or more, and 36.1% of patients had an ECOG performance status of 0. The median number of lines of prior therapy was 2 (range, 1-10), and 31.1% of patients had brain metastases at baseline.

Additional data showed that patients with baseline brain metastases who received 300 mg of sunvozertinib (n = 25) experienced an ORR of 44%.

Patients who had near loop EGFR exon 20 insertion mutations (n = 82) achieved an ORR of 52.4% with a disease control rate (DCR) of 89.0%. Specifically, patients with EGFR V769_D770insASV insertion mutations (n = 42) had an ORR of 45.2% with a DCR of 90.5%, and patients with EGFR D770_N771insSVD insertion mutations (n = 20) experienced an ORR of 70.0% and a DCR of 85.0%.

In patients with far loop EGFR exon 20 insertion mutations (n = 29), the ORR was 41.4% with a DCR of 86.2%. Patients without distinguishable EGFR exon 20 insertion mutations (n = 8) had an ORR of 25.0% with a DCR of 87.5%.

Among all patients evaluable for safety (n = 238), the most common treatment-emergent adverse effects (TEAEs) of any grade included diarrhea and rash, which were considered related to EGFR inhibition. Most TEAEs were grade 1 or 2.

The most common grade 3 or higher TEAEs reported were increased blood creatine phosphokinase (9.2%), diarrhea (5.5%), anemia (3.8%), decreased appetite (2.5%), increased lipase (2.1%), rash (1.3%), paronychia (1.3%), and nausea (1.3%).

References

1. Yang JCH, Wang M, Mitchell P, et al. Sunvozertinib in NSCLC patients with EGFR exon 20 insertion mutations. Presented at: 2022 World Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria. Abstract EP08.02-029.
2. 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 August 9, 2022. https://bit.ly/3ulggSf