ALX looks to surprise again

After surprising the markets last October with the first ever success for a CD47 inhibitor in a global randomised solid tumour study, ALX Oncology is pinning its hopes on full results from this trial, Aspen-06, to be revealed in July.

Aspen-06 tests a combo of ALX’s evorpacept in late-line HER2-positive gastric cancer, and the expected data will include duration of response plus an indication of survival. ALX remains bullish, pointing to how evorpacept has bucked the trend of failure in CD47 blockade, but the markets are unconvinced: since the start of this year ALX’s share price has halved.

Things won’t have been helped by another setback – that of the Aspen-07 study of evorpacept plus Pfizer’s Padcev in bladder cancer, presented at ASCO. That combo showed a confirmed ORR of 32%, which underwhelmed versus Padcev’s own 41% in the EV-301 trial, and ALX stock lost 16%.

This, plus evorpacept’s disappointments in myelodysplastic syndromes (Aspen-02), head and neck cancer (Aspen-01) and AML (Aspen-05), is a lot of baggage. ALX points to early successes in gastric cancer and lymphoma, and claims that evorpacept is the industry’s only CD47 project with an inactive Fc region; however, Shattuck's SL-172154 shares this feature. This could improve safety but eliminates monotherapy activity, instead relying on a combo to drive stimulation.

In Aspen-06 that stimulation comes from Herceptin: the study tests evorpacept plus Herceptin, Cyramza and paclitaxel, versus Herceptin, Cyramza and paclitaxel alone, and is what ALX describes as the largest randomised controlled trial of any anti-CD47 programme.

Last October its primary endpoint, objective response rate, came in at 52%, versus 22% for control. This result concerned responses confirmed on second scan, and ALX argued that it was highly positive on a cross-trial basis, though only 54 patients were included at the time.

Expectations

Now the company must repeat the trick, but with all 125 patients enrolled into Aspen-06’s phase 2 portion. A more mature take on response duration is also expected – a median hadn’t been reached on first analysis – and, according to a fireside chat at this month’s Jefferies healthcare conference, ALX also hopes to reveal the first signs of survival data.

The key metric investors are looking for is PFS, and Jefferies calculates that by next month median numbers should be available. ALX cites mPFS of four to six months in the Rainbow and Destiny-Gastric01 trials, and reckons the evorpacept combo beating that by “a couple of months” would amount to a meaningful result.

Still, Aspen-06’s 52% ORR isn’t far off the 41% Enhertu scored in the later-line setting of Destiny-Gastric01, and is below the 54% that Herceptin/Cyramza/paclitaxel alone scored in the RAM-HER trial. However, the latter was a South Korean study in patients after Herceptin and chemo, none of whom had received a PD-(L)1-containing western first-line standard.

Another criticism is that Aspen-06's control arm, at 22% ORR, underperformed the 28% recorded by Cyramza plus paclitaxel in the Rainbow trial, though ALX argues that that study predated the now widespread use of PD-1 blockade.

With gastric cancer patients now often receiving an anti-PD-1 MAb in the front line Aspen-06 might represent a tougher setting than Rainbow, as many of the Aspen-06 subjects will have progressed after Keytruda, and some might even have had Enhertu. 

ALX says that if the final Aspen-06 data hold up they would support US filing, but reckons the results are more important in broadly backing an evorpacept combo. As such two bigger uses currently under study could come into play: colorectal cancer, with an Erbitux combo, and an Enhertu combo in breast cancer.

The latter setting could yield data at December’s San Antonio Breast Cancer conference from the multi-cohort I-Spy-P1 study, but as this is an academic trial ALX has no control over the timing. Before then the company must beat the odds and show that Aspen-06 wasn’t a fluke.

What to look for in Aspen-06 full analysis

Source: OncologyPipeline.