FDA Grants Breakthrough Therapy Designation to Furmonertinib for EGFR Exon 20 Insertion+ NSCLC

The FDA has granted breakthrough therapy designation to furmonertinib (AST2818) for use as a potential therapeutic option in patients with previously untreated, locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations.¹

The decision is based on interim data from the phase 1b FAVOUR trial (NCT04858958) in which the agent elicited a confirmed objective response rate (cORR) of 78.6% (95% CI, 59.05%-91.70%) by independent review committee (IRC) assessment in treatment-naïve patients treated with a daily dose of 240 mg. In this group, 78.6% of patients experienced a partial response (PR) and 21.4% had stable disease (SD).²

In previously treated patients who received furmonertinib at daily doses of 240 mg and 160 mg, the cORRs were 46.2% (95% CI, 26.59%-66.63%) and 38.5% (95% CI, 20.23%-59.43%), respectively. In the previously treated 240-mg cohort, the PR and SD rates were 46.2% and 46.2%, respectively; in the previously treated 160-mg cohort, these rates were 38.5% and 46.2%, respectively.

“This FDA designation underscores the encouraging clinical activity we have seen with furmonertinib in the FAVOUR study and reflects the critical need for effective and tolerable therapeutic options for these patients,” Stuart Lutzker, co-founder and president of R&D at Arrivent Biopharma, Inc., stated in a press release.¹

The randomized, open-label, multicenter FAVOUR trial enrolled patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations who are at least 18 years of age, have at least 1 measurable lesion, and an ECOG performance status of 0 or 1.² Notably, those with asymptomatic stable central nervous system metastases were permitted.

Study participants who were treatment naïve (n = 30) received furmonertinib at 240 mg daily. Previously treated patients were randomly assigned to 1 of 2 cohorts: those who would receive the agent at 240 mg daily (n = 30) and those who would receive the agent at 160 mg daily (n = 30). Treatment continued until progressive disease (PD), unacceptable toxicity, or death.

Investigators followed patients until PD every 6 weeks; after PD, or new treatment was initiated, they were followed every 12 weeks.

In the treatment-naïve cohort, the median age was 61.5 years (range, 33-73) and most patients were female (63%), had stage IV disease (93%), and an ECOG performance status of 1 (70%). Seventeen percent had a history or the presence of brain metastases. In the previously treated cohorts who received the agent at 240 mg or 160 mg had a median age of 55.5 years (range, 33-73) and 58.5 years (range, 22-77). Most patients in both cohorts were female (57% vs 61%), had stage IV disease (100% vs 96%), and an ECOG performance status of 1 (93% vs 89%). Brain metastases were present in 29% and 39% of patients, respectively. Prior chemotherapy was received by 13% of those in the treatment-naïve cohort, 96% of those in the previously treated 240-mg cohort, and 86% of those in the previously treated 160-mg cohort.

Additional data presented at the 2023 International Association for the Study of Lung Cancer World Conference on Lung Cancershowed that the disease control rate (DCR) in the treatment-naïve cohort was 100% (95% CI, 87.66%-100.00%). In the previously treated cohorts that received the agent at 240 mg and 160 mg, the DCRs were 92.3% (95% CI, 74.87%-99.05%) and 84.6% (95% CI, 65.13%-95.64%), respectively. Across the 3 cohorts, the median duration of response was 15.2 months (95% CI, 8.74-24.84), 13.1 months (95% CI, 5.62-13.80), and 9.7 months (95% CI, 5.59-NA), respectively.

Across the groups, the median maximum tumor reduction percentages were 50.9%, 54.2%, and 36.2%, respectively.

In terms of safety, furmonertinib was found to have favorable tolerability at both dose levels evaluated. Treatment-related adverse effects (TRAEs) occurred in 97%, 100%, and 89% of patients in the treatment-naïve, previously treated 240-mg, and previously treated 160-mg cohorts, respectively; these effects were grade 3 or higher in 13%, 29%, and 18% of cases, respectively. No deaths due to TRAEs occurred.

The most common TRAEs experienced across the cohorts were diarrhea (73%; 86%; 32%), anemia (43%; 25%; 14%), increased aspartate aminotransferase (27%; 25%; 36%), and increased alanine aminotransferase (23%; 25%; 29%).

In the phase 3 FURVENT trial (NCT05607550), investigators will compare the safety and efficacy of furmonertinib at 240 mg once daily and 160 once daily with that of platinum-based chemotherapy in treatment-naïve patients with locally advanced or metastatic nonsquamous NSCLC harboring EGFR exon 20 insertion mutations.³

References

1. Arrivent receives FDA breakthrough therapy designation for furmonertinib for first-line treatment of advanced or metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. News release. ArriVent Biopharma, Inc. October 30, 2023. Accessed October 31, 2023. https://arrivent.com/arrivent-receives-fda-breakthrough-therapy-designation-for-furmonertinib-for-first-line-treatment-of-advanced-or-metastatic-non-small-cell-lung-cancer-with-egfr-exon-20-insertion-mutations/
2. Han B, Zhou C, Zheng W, et al. A phase 1b study of furmonertinib, an oral, brain penetrant, selective EGFR inhibitor, in patients with advanced NSCLC with EGFR exon 20 insertions. Presented at: International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer; September 9-12, 2023; Singapore. Abstract OA03.04.
3. Study to compare furmonertinib to platinum-based chemotherapy for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) exon 20 insertion mutations (FURVENT). ClinicalTrials.gov. Updated October 30, 2023. Accessed October 31, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05607550