Astra takes Steap2 into human trials

AZD0754, which 18 months ago was revealed as the first fruit of AstraZeneca’s stealthy in-house Car-T work, has just entered the clinic. New listings on the clinicaltrials.gov registry reveal that the Apollo study of this asset, which targets Steap2 and is additionally armoured with dominant-negative TGFβRII, started enrolment on 19 February.

New listings disclosed over the past week also feature projects targeting ROR1 and Claudin6, as well as NiKang Therapeutics’ CDK2 inhibitor NKT3447. The last will be of note to followers of Pfizer and Blueprint Medicines’ work here, and is relevant in light of the entry of BeiGene’s BG-68501 into clinical trials just last week.

Though Astra was known to have been working quietly on cell therapies for some time, it was only in late 2022 that the existence of AZD0754 was revealed. In the event AZD5851, a dnTGFβRII-armoured anti-GPC3 Car, was first into the clinic, since when Astra’s cell therapy ambitions have seen the group buy Gracell for $1bn.

Perhaps the most important thing about AZD0754 and 5851 alike is that they target solid tumours. Steap2 is an antigen overexpressed in prostate cancer, and the Apollo trial will test AZD0754 in metastatic castration-resistant prostate cancer patients who have received chemo and a novel hormonal drug like Xtandi or Zytiga.

CDK2 and others

There has been interest in CDK2 inhibition since this kinase subtype emerged as a resistance mechanism arising in response to treatment with CDK4/6 inhibitors.

While Pfizer’s PF-07104091 and Blueprint’s BLU-222 are the most advanced CDK2 inhibitors, numerous others are in development. The list has now been swelled by NiKang’s NKT3447, which this month starts a phase 1 trial that includes breast cancer patients who have progressed on CDK4/6 inhibition, and others with CCNE1-amplified tumours.

Meanwhile, the Polish biotech Pure Biologics is starting a first-in-human study (technically labelled phase 0) of PBA-0405, a CD16-based NK-cell engager targeting ROR1 antigen. Other industry work on ROR1 includes Oncternal’s Car-T therapy ONCT-808 and Merck & Co’s ADC zilovertamab vedotin, acquired through the $2.8bn purchase of VelosBio.

Xencor is under the spotlight having just revealed the axing of 10% of its workforce, a streamlining that hasn’t prevented the group from advancing into phase 1 an anti-Claudin6 T-cell engager, XmAb541. OncologyPipeline shows nine clinical-stage Claudin6-targeting industry projects, of which BioNTech’s BNT211 and BNT142 are perhaps the most prominent.

Finally, Pliant Therapeutics’ work with the small-molecule integrin αvβ8/αvβ1 inhibitor PLN-101095 will be of interest to Corbus Pharmaceuticals, which is developing CRB-601, a MAb that targets integrin avβ8 and blocks its activation-inducing interaction with L-TGFβ. A US IND for CRB-601 was cleared last month.

The first-in-human study of PLN-101095 actually began last August, but it has only just been listed on clinicaltrials.gov.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 20 and 26 Feb 2024.