iTeos, and Roche's RAS mystery, start phase 1
First-in-human study listings include EOS-215 and RO7673396.
First-in-human study listings include EOS-215 and RO7673396.
Shortly after iTeos revealed the addition of the anti-TREM2 antibody EOS-215 to its pipeline, the project's first-in-human study has been listed on the clinicaltrials.gov registry. The listing cites March as the study's start, which seems earlier than iTeos had guided.
Heads will also turn at the first disclosure of Roche's RO7673396, due to enter the clinic next month; RO7673396's mechanism is undisclosed, but its clinicaltrials.gov listing suggests that the molecule could signal Roche's entry into the pan-RAS ring. That's an area seeing increasing competition, in contrast to TREM2, where EOS-215 is the only cancer project.
This paucity of development interest is at odds with a pharmacology that some claim could hold the key to unlocking resistance in the tumour microenvironment. According to iTeos's disclosure earlier this month an IND had only just been submitted for EOS-215, and phase 1 wasn't due to begin until the second quarter.
The only other clinical-stage anti-TREM2 MAb is PY314, in development at Foundery Immune Studio, but that's not in oncology, and follows the project's jettisoning by Ikena Oncology, which in turn had acquired PY314 through the all-stock takeover or Pionyr Immunotherapeutics. In a related space SignaBlok is to present preclinical data on a TREM1 inhibitor at next month's AACR.
Pan-RAS?
Meanwhile, in RAS inhibition the industry pipeline has been swelled by subtype-specific molecules, most notably inhibitors of KRAS G12D and G12C, and the thinking has progressed to hitting multiple RAS subtypes.
The leader here is Revolution Medicine's daraxonrasib, which by the end of this year could be in four phase 3 trials, but plenty of others are playing for a piece of the action, most notably Pfizer, BeiGene and Lilly. Now Roche might be about to enter the fray with RO7673396, a previously undisclosed project.
However, this isn't certain, and is only hinted at by RO7673396's first-in-human trial, whose inclusion criteria specify the presence of any RAS mutation. For Roche to be interested in pan-RAS blockade would make sense given the Swiss company's development of the G12C inhibitor divarasib, and last year's advancement of the anti-G12D molecule GDC-7035 into human trials.
Recently disclosed first-in-human studies*
| Project | Mechanism | Company | Trial | Scheduled start |
|---|---|---|---|---|
| LXP1788/ DBPR114 | Multikinase inhibitor | LaunXP Biomedical (ex NHRI) | Solid tumours | 31 Dec 2024 |
| 225Ac-AZD2284 | Undisclosed MAb-radioconjugate | AstraZeneca | Prostate cancer, includes testing the unconjugated MAb AZD2275, & undisclosed AZD2287 | 13 Mar 2025 |
| mRNA-4106 | Immunotherapy | Moderna | Solid tumours, +/- Opdualag | 14 Mar 2025 |
| EOS006215/ EOS-215 | TREM2 MAb | iTeos | Solid tumours, +/- Keytruda | Mar 2025 |
| RO7673396 | Possible RAS inhibitor | Roche | RASm solid tumours | 30 Apr 2025 |
Note: *projects newly listed on the clinicaltrials.gov database between 14 and 19 Mar 2025.
The latest entries on clinicaltrials.gov are also notable for featuring more progress by AstraZeneca in radioligand therapy, an approach kicked off by the company's acquisition of Fusion Pharmaceuticals a year ago.
However, the precise mechanism of Astra's latest clinical entrant, 225Ac-AZD2284, remains unclear. The phase 1 study, in prostate cancer, includes cohorts testing AZD2275, described as an "unconjugated antibody", as well as a molecule coded AZD2287; the expansion stage of the trial is said to explore the prevalence of patients' PSMA and Steap2 expression.
It seems likely that AZD2275 is AZD2284 without the actinium-225 radioisotope, and possible that AZD2275/AZD2284 and AZD2287 are MAbs against PSMA and Steap2, though it's unclear which one hits which target.
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