Sunvozertinib (DZD9008) is a rationally designed selective, irreversible EGFR exon20 insertion (exon20ins) inhibitor with wild-type EGFR selectivity. The primary objective behind the development of sunvozertinib was to overcome the constraints posed by current therapies for NSCLC. Dizal Pharmaceuticals has presented the two abstracts that are explained below.
According to the data presented at the ASCO 2023, at the data cutoff on October 17, 2022, a total of 104 subjects with over 30 EGFR Exon20 insertion subtypes were enrolled, and the last subject has been followed up for 6 months. Moreover, 97 patients were included in the efficacy analysis set. The median duration on treatment, (DoT) was 7 months, and the longest DoT throughout the study was around 19.2 months.
At a median follow-up of 5.6 months among sunvozertinib responders, 64.4% were still responding. In addition, the median duration of response was not reached, but the longest DOR for a patient was over 11.2 months. The patient was still responding at the time of the data cutoff. As per the influence of the independent review committee's (IRC) assessment, the ORR was found to be 60.8%, which met its pre-defined target with statistical significance. Out of the total patient cohort, 60.8% achieved partial responses (PRs), 26.8% showed stable disease (SD), and 6.2% experienced progressive disease (PD), resulting in an impressive disease control rate (DCR) of 87.6%.
In terms of safety results, sunvozertinib exhibited a comparable safety profile to other EGFR tyrosine kinase inhibitors, with the majority of adverse events (AEs) reported as grade 1 or 2. Noteworthy, any-grade treatment emergent AEs (TEAEs) include diarrhea (67.3%), blood CPK increase (57.7%), rash (53.8%), and anemia (49.0%). Notably, grade 3 TEAEs include blood CPK increases (17.3%), diarrhea (7.7%), and anemia (5.8%).
The other abstract (#9073) of sunvozertinib in treatment naïve NSCLC patients with EGFR Exon20 insertion mutations also revealed the data at ASCO 2023. As per the data presented, at the data cutoff on February 21, 2023, a total of 28-treatment naïve advanced NSCLC patients with EGFR exon20ins received sunvozertinib daily dosing at RP2Ds. In terms of efficacy, the best objective response rate (ORR) assessed by IRC at 200 mg and 300 mg QD was 68.4% and 78.4%, respectively. Moreover, the longest duration of treatment was more than 9.8 months, with 80% of responders ongoing, and the median duration of response (DoR), was not reached at the data cutoff.
In terms of safety results, sunvozertinib was found to be well tolerated in the first line setting. Apart from that, the most common ≥ grade 3 TEAEs included creatine phosphokinase increased (14.3%), diarrhea (3.6%), lipase increased (3.6%), and rash maculo-papular (3.6%). Most importantly, no patients discontinued the treatment due to drug-related TEAEs. To sum up, sunvozertinib delivered encouraging clinical effectiveness as a first-line treatment in advanced NSCLC with EGFR Exon20 Insertions, and these remarkable findings illuminate sunvozertinib's potential as a game-changing therapeutic option for patients in the early stages of treatment.
“What's unique about sunvozertinib is its ability to inhibit all kinds of mutational subtypes as well as their locations. It is different from other inhibitors.” –Expert Opinion.
EGFR Exon20 insertions occur in ~2% of NSCLC. Sunvozertinib sets itself apart by uniquely targeting and inhibiting various mutational subtypes across diverse locations, distinguishing itself from other inhibitors. This remarkable feature positions sunvozertinib as a game-changer in the field of mutational subtype inhibition. Furthermore, sunvozertinib exhibited striking antitumor potential in treatment-naïve NSCLC patients with EGFR Exon20 insertions while unveiling promising results in patients with EGFR sensitizing mutations following failure of EGFR TKI treatments. Eventually, these groundbreaking findings highlighted sunvozertinib's broad therapeutic potential in diverse patient populations.
Based on the above findings, it can be anticipated that sunvozertinib can be a potential treatment option for NSCLC with EGFR exon 20ins. Lastly, a Phase III randomized, multinational study (WU-KONG28, NCT05668988) is ongoing to assess sunvozertinib versus platinum-based chemotherapy in first-line EGFR Exon20 NSCLC