Results from WU-KONG6, the first pivotal phase 2 study evaluating sunvozertinib vs current available therapy for patients with non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) exon20 insertion mutations. Sunvozertinib is a selective, irreversible EGFR exon20 insertion inhibitor with wild-type EGFR selectivity.

The findings from this study were presented by lead author Mengzhao Wang, MD, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

“Sunvozertinib showed significant antitumor activity in earlier clinical studies and was granted breakthrough therapy designation by the US FDA and China CDE,” explained Dr Wang during his presentation. “Based on these results, 2 single-arm pivotal studies have been conducted in patients who have failed at least 1 line of systemic therapy: WU-KONG6 and WU-KONG1.”

A total of 104 Chinese patients were enrolled in the study. Eligible patients had received a median of 2 prior lines of therapy and displayed EGFR exon20 insertion status confirmed by a local or central laboratory. Patients received sunvozertinib 300mg once daily until discontinuation. The primary end point of the study was objective response rate (ORR) and a key secondary end point was duration of response (DOR), assessed by Blinded Independent Central Review (BICR).

Efficacy analysis included 97 patients with 30 different confirmed exon20 insertion subtypes. Patients had a median age of 58 years, Of note, 95.9% of patients (n = 93) had metastatic disease at enrollment, and 32% of patients (n = 31) had baseline brain metastasis.

At the data cutoff date of October 17, 2022, BICR analysis revealed a confirmed ORR of 60.8% (n = 59). In patients with baseline brain metastasis, the confirmed ORR was 48.5% (n = 15) in patients with brain metastasis. Researchers noted that, “Anti-tumor efficacy was observed irrespective of age, gender, smoking status, prior lines of therapies, prior onco-immunotherapies, mutation subtypes, and baseline brain metastasis.”

The median follow-up time among responders was 7.1 months, and 64.4% (n = 38) of these patients were still responding. The longest DOR was >11 months and median DOR was not reached.

The safety analysis included all 104 patients enrolled in the study. The safety profile was consistent with that of previous studies and similar to other EGFR inhibitors. The majority of treatment-emergent adverse events were grade 1 or 2 and were clinically manageable.

“In WU-KONG6 pivotal study, sunvozertinib demonstrated significant antitumor efficacy and well-tolerated safety profile in platinum-based chemotherapy pretreated NSCLC with EGFR exon20 insertion mutations,” concluded Dr Wang.

“A phase 3, randomized, multinational study, WU-KONG28, is ongoing to address sunvozertinib vs platinum-based chemotherapy in the first-line setting for EGFR exon20 insertion NSCLC,” he added.

Source:

Wang M, Fan Y, Sun M, et al. Sunvozertinib for the treatment of NSCLC with EGFR Exon20 insertion mutations: The first pivotal study results. Presented at 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. Abstract 9002