Head and neck cancer is next for evorpacept

Despite the recent addition of an anti-EGFR antibody-drug conjugate to its pipeline ALX Oncology still lists evorpacept as its lead R&D project. In the second quarter this CD47 inhibitor will yield results from two controlled phase 2 trials that could determine whether it has a future in head and neck cancer.

If the studies, Aspen-03 and 04, read out positively evorpacept will continue on its bumpy journey, though whether there exists much investor appetite to keep funding its development remains an open question. The CD47 space has seen numerous disappointments, and evorpacept's one claimed success, in late-line, HER2-positive gastric cancer, came with caveats.

Nevertheless, the company continues to tout gastric cancer as a registrational indication, and is seeking FDA input on a path to approval, based on the Aspen-06 study, which first showed positive data, then failed, and was then resurrected based on a subgroup analysis.

First-line head & neck

In head and neck cancer ALX is testing evorpacept in first-line squamous disease, and Aspen-03 and 04 broadly follow the settings in which Keytruda is FDA-approved on the basis of the Keynote-048 study.

The Merck & Co drug has a monotherapy label in PD-L1-expressing patients, and is available in first-line all-comers as part of a platinum/5FU chemo triplet. Aspen-03 and 04 concern these same respective settings, and add evorpacept on top of the relevant Keytruda regimen – with control cohorts comprising Keytruda monotherapy, and Keytruda plus chemo, respectively.

The fact these studies are controlled will allow a direct comparison, but Keynote-048 will provide a useful additional sanity check as to whether the comparator over or underperforms. The response rates (Aspen-03 and 04's primary endpoints) ALX is shooting to beat are 19% for the PD-L1-positive trial and 36% in the Keytruda/chemo triplet study.

A sign of how survival numbers are shaping up in the two studies will also be important, and both trials list PFS and OS among secondary endpoints, though it's not clear how much ALX will say about data beyond response rates. Results of Aspen-03 were once expected in mid-2024, but now data from both studies are promised in the current quarter.

Evorpacept in squamous cell head & neck cancer

Source: OncologyPipeline.

The company clearly believes that evorpacept has a chance here, and its enthusiasm is based on a first-line head and neck cancer cohort of the multi-tumour basket trial Aspen-01.

Here a Keytruda/chemo triplet gave ORR and median PFS figures of 39% and 5.6 months respectively, numerically slightly above those seen in Keynote-048. The big caveat, however, was that these came from a subset of just 13 patients in Aspen-01.

Any bullishness is clearly not shared by the markets, which at present value ALX at just $27m, well south of the company's $131m year-end cash balance. Should Aspen-03 and 04 blow up, ALX's newly revealed anti-EGFR ADC ALX2004 could provide a distraction, though at present there's nothing to suggest that investors have much enthusiasm for its development either.