World Lung 2024 – ArriVent looks for lung cancer white space
The group is going beyond EGFR exon 20 insertions, but still has work to do to justify its valuation.
The group is going beyond EGFR exon 20 insertions, but still has work to do to justify its valuation.
ArriVent Biopharma has been on the up since floating earlier this year, but its $900m valuation has seemed rich for a late arrival to the NSCLC EGFR exon 20 insertion space, where Johnson & Johnson’s Rybrevant is already well established.
On Monday at a World Lung presidential session ArriVent unveiled data that might help propel its sole clinical project, firmonertinib, into a new niche: NSCLC patients with EGFR P-loop alpha-c helix compressing (PACC) mutations. With little other industry activity here, and with PACC mutations said to be more common than exon 20 insertions, the data could bolster the group’s stock further.
Still, it’s early days: the results came from one cohort of an uncontrolled phase 1 study – albeit one sponsored by ArriVent, including US sites. Until recently firmonertinib was a predominantly Chinese project, and has also gone under the generic names furmonertinib and alflutinib.
ArriVent licensed it from Shanghai-based Allist Pharma, and the drug's China approvals for NSCLC mirror some of those of AstraZeneca's Tagrisso in the west: first-line patients with classical EGFR mutations, and in second-line patients with EGFR T790m mutations – the latter have been all but wiped out by Tagrisso in the western world.
Going Further
ArriVent already has a global phase 3 trial ongoing, Furvent, in first-line NSCLC with EGFR exon 20 insertion mutations.
But the data presented on Monday came from the phase 1 Further study, which includes various cohorts – cohort four, which featured at World Lung, involved TKI-naive subjects with EGFR PACC mutations. These are said to represent 12% of all EGFR mutations, versus 9% with exon 20 insertions.
Firmonertinib was dosed at 160mg or 240mg once daily, and the primary endpoint was ORR by independent review. At a 20 June 2024 cutoff the results appear to show a dose response. They also stack up well against the 30-40% ORR that, according to ArriVent, has been seen with other TKIs in PACC-mutated disease.
Phase 1 results in TKI-naive EGFR PACC mutated patients
| 160mg/day | 240mg/day | |
|---|---|---|
| Confirmed ORR | 35% (8/23 PRs) | 64% (14/22 PRs) |
| Confirmed + unconfirmed ORR | 48% (11/23 PRs) | 82% (18/22 PRs) |
| TRAEs (any grade) | 84% (26/31) | 86% (25/29) |
| Grade ≥3 TRAEs | 13% (4/31) | 21% (6/29) |
| Dose interruption | 19% (6/31) | 34% (10/29) |
| Dose reduction | 13% (4/31) | 24% (7/29) |
| Discontinuation | 0 | 0 |
Note: results measured using blinded independent central review. Source: IASLC & Dr Jie Wang.
Median duration of response hasn’t been reached, with 20 of 22 responders still on therapy; PFS and OS data are still immature.
As for adverse events, it will be worth keeping an eye on diarrhoea and liver enzyme elevations in future readouts; 10% of high-dose patients had grade 3 diarrhoea, while 7% had grade 3 liver enzyme elevations. No grade 4 or 5 treatment-related adverse events were seen.
There were also no discontinuations in cohort four; however, there was a 5% dropout rate in the 240mg group in the wider Further trial.
The PACC pack
If ArriVent can replicate these data in a larger controlled trial it might be able to find a way to differentiate in the crowded EGFR inhibitor field.
The company claims that Further is the first prospectively designed and randomised global study in PACC mutations. A search of OncologyPipeline shows an investigator sponsored trial of Boehringer’s Gilotrif in NSCLC with EGFR PACC mutations, but no other specific trials in this niche.
Still, it seems possible that, if firmonertinib works here, other EGFR inhibitors will, too. Indeed, some investigators have suggested that patients with PACC mutations respond better to second-generation versus first or third-generation TKIs. ArriVent will need to make the most of its head start.
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