Sunvozertinib (brand name Zegfrovy) is an oral prescription medicine used to treat adults with advanced non-small cell lung cancer (NSCLC) that has an abnormal EGFR gene, specifically an exon 20 insertion mutation, while sparing wild-type EGFR relatively.
Approved for adults with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations (detected by an FDA-approved test, the Oncomine Dx Express Test) whose disease has progressed on or after platinum-based chemotherapy.
Treats locally advanced or metastatic (spreading) lung cancer.
The recommended dose is 200 mg orally once daily with food until disease progression or unacceptable toxicity.
Tablets must be swallowed whole; not chewed, crushed, or split.
WU-KONG1B trial, the primary efficacy population of 85 patients treated at 200 mg once daily had a confirmed objective response rate (ORR) of 46% with a duration of response of 11.1 months.
The broader dose-randomized analysis showed comparable efficacy at 200 mg and 300 mg, but a more favorable safety profile at 200 mg.
First-line data (WU-KONG28, phase 3): In previously untreated patients randomized to sunvozertinib vs. carboplatin-pemetrexed chemotherapy, sunvozertinib significantly improved median progression-free survival (10.3 vs. 7.5 months; and ORR (58.9% vs. 31.1%).
Adverse events reflect on-target EGFR inhibition.
In the first-line phase 3 trial, grade ≥3 adverse events occurred in 75.5% of sunvozertinib patients, with the most common being increased serum creatine kinase (20.9%), diarrhea (14.1%), and anemia (9.2%).
Diarrhea (all grades) occurred in 87%, and rash and paronychia were also frequent.
The prescribing information carries warnings for: Interstitial lung disease/pneumonitis (led to discontinuation in ~1.8% and was the most common cause of discontinuation in WU-KONG6, ~5–6% with ILD).
Gastrointestinal adverse reactions (diarrhea)
Dermatologic adverse reactions
Ocular toxicity
Embryo-fetal toxicity
Fatigue
QTcF prolongation >500 msec with an increase >60 msec from baseline was reported in 1.8%.
Serious lung inflammation (pneumonitis or interstitial lung disease) can occur in rare cases.
Sunvozertinib as an option for EGFR exon 20 insertion NSCLC.
The efficacy of sunvozertinib is superior to that of chemotherapy is first line treatment for advanced NSCLC with EGFR exon 20 insertions.