First-line firmonertinib produced responses in 68% of patients with EGFR PACC-mutant NSCLC at 240 mg

A structurally distinct EGFR subgroup with limited treatment options

The authors describe PACC mutations as a structurally distinct subgroup of EGFR mutations in NSCLC, and patients who carry them have limited treatment options. The paper pairs laboratory work on firmonertinib with first-line clinical data from the FURTHER study.

Firmonertinib is a brain-penetrant, mutant-selective EGFR inhibitor with a trifluoroethoxy side chain unique to the molecule. In EGFR PACC-mutant cell lines and xenograft models, it showed high anti-proliferative efficacy.

Responses in 68% of patients at 240 mg, against 43% at 160 mg

Both figures are confirmed objective response rates in first-line metastatic disease, measured in arms of 22 patients (240 mg) and 25 patients (160 mg). Patients were randomised between two doses of the same drug, so the study has no comparator arm of another EGFR inhibitor or of chemotherapy.

The median duration of response was 14.6 months in the 240 mg arm. In the 160 mg arm the median had not been reached when the data were reported, so the two arms cannot yet be compared on this endpoint.

Median progression-free survival of 16.0 months at the higher dose

Patients given 240 mg had a median progression-free survival of 16.0 months, 4.9 months longer than the 11.1 months observed with 160 mg. The abstract gives no hazard ratio or p value for the comparison between doses, and each arm holds fewer than 30 patients.

Intracranial responses in eight of 17 patients with brain metastases

Among patients with brain metastases at baseline, eight of 17 had an intracranial objective response, a rate of 47%. The investigators had described firmonertinib as brain-penetrant, and this is the clinical figure reported for that property in the trial.

Dose reductions in about a fifth to a quarter of patients, and few discontinuations

Treatment-related adverse events led to a dose reduction in 19% of patients at 160 mg and 24% at 240 mg. They led to discontinuation in 3% and 0% of patients, respectively. The higher dose, which produced the higher response rate and the longer median progression-free survival, did not lead more patients to stop treatment.

“Results support further study of first-line firmonertinib in patients with EGFR PACC-mutant NSCLC.”Le et al., Cancer Cell (2026)

Phase 1b evidence from 47 randomised PACC patients

The efficacy results come from 47 patients randomised between two doses in a phase 1b study. The authors present them as grounds for further study of first-line firmonertinib in this population.

The 240 mg arm had the higher response rate and the longer median progression-free survival, with no discontinuations for treatment-related adverse events. The abstract does not compare firmonertinib with any other treatment for PACC-mutant disease.