Dizal breaks new ground for EGFR drugs in lung cancer

Dizal Pharmaceutical's Zegfrovy has taken the EGFR inhibitor class into new territory after hitting the mark in a phase 3 trial as a first-line treatment for non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations.

The readout of the WU-KONG28 study showed a statistically significant improvement in progression-free survival (PFS) with Zegfrovy (sunvozertinib) monotherapy over a platinum-based chemotherapy regimen, offering the prospect of becoming the first "oral, once daily, chemo-free, targeted therapy" for these patients, according to the company.

At the moment, the only drug approved in the front-line setting for this niche category of EGFR-mutated NSCLC is Johnson & Johnson's intravenously administered Rybrevant (amivantamab) in combination with chemo, so the WU-KONG 28 data give China-based Dizal a shot at providing a more patient-friendly and healthcare resource-sparing alternative.

Orally-active, tyrosine kinase inhibitor-based EGFR drugs, including AstraZeneca's market-leading Tagrisso (osimertinib), have struggled to show efficacy against this type and are used mainly to treat tumours with exon 19 and 21 mutations. NSCLC driven by exon 20 mutations tend to carry a worse prognosis and shorter survival times.

"Finding a drug targeting EGFR exon 20 insertion mutations is especially challenging due to their enormous heterogeneity," said Dr Xiaolin Zhang, Dizal's chief executive.

"Despite tremendous efforts, there is no success yet in finding an effective target drug that can spare patients from chemotherapies," he added. "WU-KONG28 study has the potential to change all that."

Data from WU-KONG28 hasn't been revealed yet, but will be presented at an oncology meeting in the coming months. Dizal said it also intends to discuss the results with regulatory authorities to see if it can support regulatory filings.

Zegfrovy claimed accelerated approval from the FDA last July as a second-line or later therapy for NSCLC with EGFR exon 20 insertions in patients whose cancer has progressed on or after platinum-based chemo, and has also been cleared for this indication in China. It is the only orally active drug approved as a monotherapy for these patients, after Takeda's Exkivity (mobocertinib) was withdrawn from sale for failing a confirmatory trial.

Other oral drugs are being tested as first-line therapy for NSCLC patients with EGFR exon 20 insertions, including ArriVent Biopharma's furmonertinib, licensed from China's Allist, which is in the phase 3 FURVENT trial and due to generate results in the first half of this year.