ArriVent goes Further into PACC mutations

After ArriVent last year signalled its intent in a new non-small cell cancer genetic subtype, EGFR PACC mutations, the company is pushing into phase 3 here with its EGFR inhibitor firmonertinib. The upcoming front-line Alpacca study could support an FDA accelerated approval based on overall response rate, ArriVent said during an investor call on Monday.

Meanwhile progression-free survival data will be used to back full approval, if positive. Still, it seems that the need for a pivotal trial with an active comparator caught investors unaware, with ArriVent stock closing down 10% on Monday.

The group’s backers might have been hoping for an easier path to the US market in the PACC mutation niche. Nothing is specifically approved here, although AstraZeneca’s Tagrisso and Boehringer’s Gilotrif are used, according to ArriVent, which licensed firmonertinib from China's Allist Pharma. 

Beyond this ArriVent doesn’t have too much competition here, although Black Diamond has shown promise with its fourth-generation EGFR inhibitor BDTX-1535 – albeit in post-Tagrisso patients.

But the company looks likely to need more cash before Alpacca reads out. At the last count, ArriVent had $205m in the bank, enough to get it into the second half of 2026.

Going Further

EGFR PACC (P-loop alpha-c helix compressing) mutations are said to be seen in around 3% of non-squamous NSCLC patients. Firmonertinib first showed promise here last September, when data from the front-line PACC mutant cohort of the phase 1 Further trial were presented at the World Lung meeting.

On Monday ArriVent presented more results from this global study, showing improving response rates and, for the first time, median progression-free survival data: 16.0 months with the go-forward dose, 240mg per day. According to ArriVent, this compares well to historical data with Tagrisso and Gilotrif, which produced median PFS of 9.4 months in the Unicorn trial, and 10.6 months in the Achilles study respectively.

Phase 1 results for firmonertinib in first-line EGFR PACC mutated NSCLC

Note: efficacy results, in 1st-line only, measured using blinded independent central review; safety data across all PACC pts. Source: IASLC & company presentation.

In the phase 3 Alpacca study, to begin in the second half and enrol around 480 patients, firmonertinib 240mg daily will go up against investigator’s choice of Tagrisso or Gilotrif. When asked why chemo wasn’t being included as a potential comparator, ArriVent’s president of R&D, Stuart Lutzker, noted that Tagrisso and Gilotrif were recommended by NCCN guidelines for patients with PACC mutations, but chemo wasn’t. 

He added that the decision to use Tagrisso or Gilotrif as control was made after discussions with the FDA. ArriVent execs didn’t say when the ORR results might be available.

Firmonertinib is separately in a phase 3 in first-line NSCLC patients with exon 20 insertion mutations, Furvent; here enrolment is complete and data are due this year. 

Notable firmonertinib trials

Source: OncologyPipeline & company presentation.