AstraZeneca debuts ZEGFROVY in US lung cancer

AstraZeneca (AZN) has begun US commercial availability of ZEGFROVY (sunvozertinib) for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 20 insertion mutations and whose disease has progressed on or after platinum-based chemotherapy. The medicine is administered orally as a 200 mg dose once daily with food and is distributed through a dedicated ZEGFROVY Specialty Distribution and Pharmacy network, with availability also through health system specialty pharmacies.

ZEGFROVY is described as the only approved oral, single-agent targeted therapy in the US for this patient group following platinum-based chemotherapy. The indication requires that EGFR exon 20 insertion mutations be detected using an FDA-approved test before treatment.

The US Food and Drug Administration granted accelerated approval to ZEGFROVY based on results from the WU-KONG1B trial, a multinational, open-label, dose-randomization study. In an efficacy population of 85 patients treated with ZEGFROVY 200 mg once daily, the confirmed overall response rate was 46%.

Among the 39 patients who responded, the median duration of response was 11.1 months. Seventy-two percent of these responders maintained their response for at least six months. Continued approval for this indication may depend on confirmation of clinical benefit in a separate confirmatory trial.

The safety population included 121 patients, in whom diarrhea occurred in 73% of patients, including 2.5% with Grade 3 events. Serious gastrointestinal adverse reactions were reported, as were ocular toxicities such as keratitis and visual disturbances in a subset of patients.

EGFR exon 20 insertion mutations represent a distinct subset of EGFR-mutated NSCLC, and five-year overall survival for these patients can be as low as 8%.

Sunvozertinib is included in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for NSCLC as a Category 2A recommended subsequent therapy option for patients with advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations. This positions the medicine as a guideline-recognized treatment choice after prior therapy.

Product information for ZEGFROVY highlights the risk of severe and life-threatening interstitial lung disease or pneumonitis. The drug can also cause severe gastrointestinal adverse reactions, including diarrhea, nausea and vomiting, and severe rash such as acneiform dermatitis and pruritus.

Ocular toxicity, including keratitis, dry eye, blurred vision and visual impairment, has been observed, with ocular events reported in 13% of patients in the safety population and keratitis in 0.8%. The medicine may cause fetal harm when administered during pregnancy, and prescribers are advised to monitor and manage these risks during treatment.

AstraZeneca has submitted a Supplemental New Drug Application in the US and a corresponding filing to China’s Center for Drug Evaluation seeking approval of ZEGFROVY in the first-line setting, supported by Phase III WU-KONG28 trial results. Both regulators have granted Breakthrough Therapy Designation for this proposed first-line use, and the applications remain under review.

Both regulators have granted Breakthrough Therapy Designation for this setting.