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A new approach to treating a rare form of lung cancer is showing real promise. In a Phase 1b trial, firmonertinib achieved meaningful tumor shrinkage and durable responses in patients with EGFR PACC-mutated non-small cell lung cancer (NSCLC) — a subgroup that has historically lacked good treatment options. The findings, published in Cancer Cell, are now fueling a global Phase 3 trial.
Researchers at MD Anderson Cancer Center are making the case that understanding the structure of a cancer mutation — not just its location — could be the key to better treatment decisions. In a Phase 1b trial called FURTHER, the targeted therapy firmonertinib showed durable antitumor activity in patients with EGFR PACC-mutated NSCLC, a structurally distinct subgroup that accounts for roughly 12% of EGFR-mutant lung cancers but has long been underserved by existing therapies.
The trial enrolled 60 patients with advanced disease. Among previously untreated patients, firmonertinib produced objective response rates of 43% at the lower dose and 68% at the higher dose — with responses seen across multiple PACC mutation subtypes. Notably, 47% of patients with brain metastases saw tumor shrinkage in the brain, including 41% who achieved complete responses.
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Why it matters: These results offer a new treatment pathway for a patient population with historically limited options, and they validate a structure-guided approach to therapy selection. The findings have already prompted the launch of the global Phase 3 ALPACCA trial, comparing firmonertinib head-to-head against standard-of-care options.
