NEWTOWN SQUARE, PA — ArriVent BioPharma Inc. (Nasdaq: AVBP) reported a 68% tumor response rate and median progression-free survival of 16 months at the higher dose of its experimental lung cancer drug firmonertinib, strengthening the clinical evidence behind an ongoing Phase 3 trial targeting patients with an uncommon genetic mutation.
The findings, published in the scientific journal Cancer Cell, come from the company’s Phase 1b FURTHER study of previously untreated patients with advanced non-small cell lung cancer carrying EGFR PACC mutations.
The results support ArriVent’s development of firmonertinib as a potential oral treatment for a patient population without an established targeted standard of care.
EGFR PACC mutations account for approximately 12% of EGFR-mutant lung cancers. Patients with these mutations have limited treatment options because existing therapies were not specifically developed to target their molecular characteristics.
At the 240-milligram dose, firmonertinib produced a confirmed overall response rate of 68%, with median progression-free survival of 16 months, according to blinded independent central review.
Patients receiving the 160-milligram dose had a confirmed response rate of 43% and median progression-free survival of 11.1 months.
Progression-free survival measures the length of time patients remain alive without their cancer worsening. Overall response rate measures the proportion of patients whose tumors shrink by a predefined amount.
The findings also indicated activity against cancer that had spread to the brain, a significant complication in advanced lung cancer.
Among 17 patients with brain metastases at the beginning of treatment, eight achieved confirmed intracranial responses, representing 47% of the group. Complete intracranial responses were reported in 41% of those patients.
Researchers also examined circulating tumor DNA, or ctDNA, to assess whether molecular changes during treatment were associated with clinical outcomes.
Among evaluable patients, 80% achieved complete molecular response by the third treatment cycle.
Patients whose ctDNA cleared had a 70% overall response rate, compared with 20% among those without clearance. Median progression-free survival was 15.1 months versus three months, respectively.
The findings suggest that early molecular response could help identify patients more likely to benefit from treatment, although the association does not establish ctDNA clearance as a validated predictor of clinical benefit.
Laboratory studies included in the publication also found that firmonertinib demonstrated greater activity against PACC-mutated EGFR than osimertinib, an established EGFR-targeted therapy.
Researchers attributed the difference to firmonertinib’s molecular structure, which provides additional binding interactions within the mutated EGFR kinase domain.
Xiuning Le, an associate professor of thoracic and head and neck medical oncology at the University of Texas MD Anderson Cancer Center, said the laboratory findings were supported by the clinical observations.
“Now the preclinical findings translated to prospective clinical trial data, resulting in robust confirmed response and progression-free survival,” Le said.
ArriVent reported that treatment-related adverse events were consistent with firmonertinib’s safety profile in previous clinical studies.
The company is now enrolling patients in its global Phase 3 ALPACCA trial, which is evaluating firmonertinib against investigators’ choice of osimertinib or afatinib as initial treatment for locally advanced or metastatic EGFR PACC-mutant non-small cell lung cancer.
The randomized comparison will provide further evidence about firmonertinib’s effectiveness relative to existing treatment options.
“We believe firmonertinib has the potential to change the treatment paradigm for EGFR PACC-mutant NSCLC, and these findings give us a strong foundation for our global Phase 3 ALPACCA trial,” said Bing Yao, ArriVent’s chief executive officer.
Firmonertinib is an oral EGFR inhibitor designed to target both common and uncommon mutations associated with non-small cell lung cancer, including PACC and exon 20 insertion mutations.
The drug is already approved in China for certain forms of EGFR-mutant non-small cell lung cancer, including specified patients with classical EGFR mutations and previously treated patients with exon 20 insertion mutations.
In the United States, firmonertinib has received Food and Drug Administration Breakthrough Therapy Designation for previously untreated, locally advanced or metastatic nonsquamous non-small cell lung cancer with EGFR exon 20 insertion mutations.
It has also received FDA Orphan Drug Designation for non-small cell lung cancers involving EGFR, HER2 or HER4 mutations.
Those designations do not constitute FDA approval. Firmonertinib remains investigational in the United States.
Non-small cell lung cancer accounts for approximately 85% of lung cancer cases. EGFR mutations are among the genetic alterations that can drive tumor growth, making them targets for precision medicines.
The Phase 1b FURTHER study is registered under ClinicalTrials.gov identifier NCT05364073. The ongoing Phase 3 ALPACCA trial is registered as NCT07185997.
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