Antitumor activity of sunvozertinib in NSCLC patients with EGFR Exon20 insertion mutations after platinum and anti-PD(L)1 treatment failures.

9015 Background: Platinum-based chemotherapy is the 1st line standard of care for NSCLC patients with EGFR exon 20 insertion mutations (Exon20ins), with anti-PD(L)1 frequently used as well. Here we present anti-tumor activity of sunvozertinib in these patients whose disease had progressed on these therapies from two ongoing phase 1/2 studies (WK-KONG1, NCT03974022 and WU-KONG2, CTR20192097). Based on these data, sunvozertinib was granted the Breakthrough Therapy Designation by both US FDA and China NMPA. Methods: The objective of this study is to characterize the safety and efficacy of sunvozertinib in platinum-pretreated advanced NSCLC patients harboring EGFR Exon20ins, with or without anti-PD(L1) treatment. In addition, the effect of prior treatment on sunvozertinib’s safety and efficacy were explored. Results: As of July 30, 2021, a total of 52 locally advanced or metastatic NSCLC patients harboring EGFR Exon20ins post platinum treatment were enrolled into WU-KONG1 and WU-KONG2 studies, and included in the efficacy analysis set (dose range: 50 mg to 400 mg, once daily). Male/Female: 21/31; Median age 59; Asian/White: 44/8; Prior therapies: median 2.5 (range 1-10); 31% received prior anti-PD(L)1 treatment (all in £ 300 mg cohorts); 40% of the subjects with baseline brain metastasis. Partial response was observed at ≥ 100 mg. At the dose level of 100 mg, 200 mg, 300 mg and 400 mg, confirmed ORR was 50% (1/2), 55.6 % (5/9), 44.8% (13/29) and 22.2% (2/9), respectively. With a median follow-up time of 10.5 months, median DoR was not reached for 200 mg cohort; with a median follow-up of 7 months, median DoR of 300 mg group was 5.6 months. Progression free survival (PFS) rate at 6 months for 100 mg, 200 mg, 300 mg and 400 mg cohorts was 50%, 53.3%, 44.6% and 44.4%, respectively. In patients with/without prior anti-PD(L)1 treatment, comparable efficacy and safety profiles were observed. Conclusions: The data suggest sunvozertinib is active in platinum-pretreated patients with EGFR Exon20ins, irrespective of prior or after anti-PD(L)1 treatment. The updated data will be presented at the meeting. Sunvozertinib is currently in phase 2 pivotal clinical development (NCT03974022 and China CTR20211009). Clinical trial information: NCT03974022.