Dive Brief:
- Taiho Oncology and partner Cullinan Therapeutics said a targeted medicine they’re developing has succeeded in a Phase 3 trial in frontline lung cancer, with investigators halting the study at an early data check because of clearly positive results.
- Taiho and Cullinan have been testing that therapy, zipalertinib, alongside chemotherapy in the first-line setting in people whose lung tumors have a so-called exon 20 insertion in a gene called EGFR. They didn’t release detailed data, but on Wednesday said that the combination “demonstrated a statistically significant and clinically meaningful improvement” in progression-free survival, meeting a pre-planned threshold for unblinding the trial.
- The Food and Drug Administration is already reviewing zipalertinib as a second-line treatment and is expected to make a decision by Feb. 27. If approved, the drug will add to an already competitive market battle. Johnson & Johnson’s Rybrevant and AstraZeneca and Dizal’s Zegfrovy are both available, and another biotechnology company, ArriVent BioPharma, is expecting Phase 3 data later this year.
Dive Insight:
EGFR exon 20 insertion mutations are present in only a small fraction of lung cancers. EGFR mutations broadly account for about 10% to 15% of lung tumors in the U.S. And these particular exon 20 alterations are seen in anywhere from 1% of 10% of those cases, according to the American Lung Association. (Some estimates show that the prevalence is higher among people in China, women and non-smokers.)
Still, targeted medicines for these tumors can be big business opportunities. AstraZeneca’s Tagrisso, which treats different EGFR mutations, surpassed $7 billion in sales last year. J&J’s Rybrevant franchise, used on exon 20 insertions and other EGFR mutations, pulled in more than $700 million in 2025. AstraZeneca recently promised China-based Dizal up to $1.5 billion for Zegfrovy rights, while Taiho in 2022 bought back partial rights to zipalertinib for up to $405 million.
Taiho and Cullinan asked for an approval in the second-line setting based on a Phase 2 trial in which zipalertinib shrank or eliminated tumors in more than one-third of the patients who received it. The Phase 3 trial in first-line disease is comparing zipalertinib and chemo to chemo and a placebo. The combination’s goal is to delay progression or death.
Although the partners didn’t release detailed data, William Blair analyst Matt Phipps wrote that the trial was powered to show a 40% reduction in the relative risk of tumor progression or death at a final analysis. That design suggests investigators saw an even bigger effect at an interim data check, he wrote.
Phipps added that, when tested as a monotherapy against chemo, Zegfrovy has reduced the risk of progression by 35%.
Taiho and Cullinan’s readout also “raises the competitive bar” for ArriVent, which is expecting pivotal data for its drug firmonertinib in the next few months, wrote Cantor Fitzgerald analyst Li Watsek. ArriVent shares dipped as much as 7% in morning trading, but Watsek cautioned that it is “premature to assess the magnitude of the competitive threat.”
Additionally, Watsek argued that the relative safety profiles of each drug may be the key differentiating factor for patients and physicans. ArriVent is comparing firmonertinib monotherapy to chemo in its Phase 3 trial which, if successful, could yield an alternative with fewer side effects, she added.
