Firmonertinib Shows Promise in Rare EGFR Mutated Lung Cancer, Trial Finds

An experimental targeted therapy has shown promising activity in patients with a rare form of Non-Small-Cell Lung Cancer (NSCLC), with a clinical trial reporting prolonged disease control and responses in brain metastases.

The Phase 1b FURTHER trial, led by researchers at The University of Texas MD Anderson Cancer Center, found that firmonertinib produced durable antitumour activity in patients with EGFR PACC mutated NSCLC. The findings support selecting treatments according to the structural features of uncommon EGFR mutations.

The study published in Cancer Cell on 16th October 2026, the results showed that patients receiving daily doses of 160 mg and 240 mg had median progression-free survival of 11.1 months and 16 months, respectively. Progression-free survival measures how long patients live without their disease worsening.

The trial was led by Xiuning Le, associate professor of Thoracic/Head and Neck Medical Oncology at MD Anderson.

“Patients with uncommon EGFR mutations have long faced limited evidence to guide treatment decisions,” Le said. “The responses we observed with firmonertinib in patients with EGFR PACC mutations are encouraging and suggest that understanding mutation structure may help identify therapies better matched to a patient’s cancer.”

PACC mutations are a structurally distinct subgroup of EGFR mutations that account for approximately 12% of EGFR mutated NSCLC. Treatment responses can differ from those seen with more common mutations.

Researchers have proposed classifying uncommon EGFR mutations according to how they change the structure of the EGFR protein, rather than relying solely on their location within the gene. This approach may better predict which therapies will be effective.

The study found that a unique chemical feature of firmonertinib enables it to bind more effectively to EGFR proteins carrying PACC mutations.

In preclinical models, firmonertinib demonstrated potent antitumour effects across multiple PACC mutation subtypes. Tumour growth inhibition frequently exceeded 90% in laboratory and patient-derived xenograft models.

The global FURTHER trial enrolled 60 patients with advanced EGFR PACC mutated NSCLC. Among previously untreated patients, objective response rates were 43% with 160 mg daily and 68% with 240 mg daily. Responses occurred across multiple PACC mutation subtypes, including single and compound mutations.

Researchers also assessed circulating tumour DNA (ctDNA), fragments of tumour-derived DNA found in the bloodstream that can help monitor treatment response without invasive procedures. Among evaluable patients, 80% achieved complete clearance of EGFR PACC mutations from their blood after treatment. Patients with ctDNA clearance generally experienced higher response rates and longer progression-free survival, suggesting that changes in ctDNA could help identify those most likely to benefit.

The therapy also showed activity against brain metastases, a common complication of EGFR mutated lung cancer, including lesions that had not previously been treated with radiation therapy. Of the 17 patients with brain metastases at the start of treatment, 47% experienced tumour shrinkage in the brain, while 41% achieved complete responses.

The findings prompted the launch of the global Phase 3 ALPACCA trial, which is evaluating firmonertinib against osimertinib or afatinib as a first-line treatment for patients with advanced EGFR PACC mutated NSCLC.

Further research will investigate ctDNA as a potential biomarker of treatment response, examining whether changes in these DNA fragments can help monitor outcomes and inform treatment decisions.