Acrivon CHKs itself

First, the good news for Acrivon: the company still hopes to pursue accelerated approval of its CHK1/2 inhibitor ACR-368 based on phase 2 data in relapsed endometrial cancer, which it updated on Tuesday after market.

The bad news, though, is that response rates have dwindled since the company’s last update, at ESMO. And Acrivon has also thrown in the towel in ovarian and bladder cancers. The company’s share price closed down 52% on Wednesday.

Testing

According to Acrivon, ACR-368 looked uncompetitive in ovarian cancer, and in bladder cancer it wasn’t able to identify enough potential responders.

This highlights a further complication with Acrivon’s approach: the phase 2 trial included testing at baseline with the group’s Oncosignature assay, to divide patients into likely responders (so-called BM+) and non-responders (BM-).

BM+ patients went on to receive ACR-368 monotherapy, while BM- patients got ACR-368 in combination with low-dose gemcitabine. It’s the BM+ patients that could provide a route to early approval.

Here, Acrivon highlighted a 35% ORR among 20 patients; these had a median of two prior lines of therapy, and had all previously received PD-(L)1 inhibitors. On the face of it this looks much better than the 12% ORR that the company cited with current standard of care in second-line endometrial cancer.

However, response rates have dropped since last year’s ESMO meeting, when Acrivon reported an ORR of 63%, albeit in just eight patients.

Evolving endometrial cancer data from phase 2 trial of ACR-368

Source: OncologyPipeline & company presentations.

Response rates in BM- patients look less promising, but in any case Acrivon highlighted that this was an exploratory combination.

It’s unclear how much more data Acrivon will need for a filing in second-line-plus endometrial cancer; according to the company’s presentation the next steps will be to provide updates on the current study, said to have "registrational intent", and confirmatory trial design.

ACR-368, known generically as prexasertib, is the only clinical-stage CHK1/2 inhibitor, but there are plenty of other groups developing CHK1 blockers, including Boundless Bio, which went public last year.

Prexasertib was originally discovered by Array BioPharma, and later licensed to Lilly; the latter shelved the project in 2019, and Acrivon licensed it in 2021. 

Wee1 & PKMYT1 

Acrivon is also developing a dual Wee1 and PKMYT1 inhibitor, ACR-2316. The only company with a similarly acting project is Schrödinger, with SGR-3515, although other groups have tried hitting these targets separately – in the case of Wee1 without much success.

Acrivon also released results from a phase 1 trial of ACR-2316, although these mainly involved biomarker data. The company said its first two doses had been cleared without any safety concerns, and that dose-level three was now fully enrolled.