ART0380

Overview

ART0380 (IACS‑030380) is an oral, selective ATR kinase inhibitor being developed by Artios Pharma for advanced solid tumors. It is being studied as monotherapy and in combinations that increase replication stress (notably low‑dose irinotecan and gemcitabine). As of 2025, first clinical signals include objective responses in biomarker‑selected populations (particularly ATM‑deficient cancers), and a tolerability profile consistent with on‑target effects of ATR inhibition. (pubs.acs.org)

Mechanism of action

• Target: Ataxia telangiectasia and Rad3-related (ATR), a master regulator of the DNA replication‑stress response and S‑phase checkpoint. Inhibition of ATR prevents DNA damage checkpoint activation and sensitizes tumor cells—especially those with high replication stress or defects in complementary DDR pathways (e.g., ATM loss)—to DNA damage and replication fork collapse. (pubs.acs.org)
• Molecule: Medicinal chemistry characterization describes ART0380 as a potent, selective ATR inhibitor with human PK supportive of both intermittent and continuous once‑daily dosing and low interpatient variability. (pubs.acs.org)

Efficacy

Clinical data to date come from early‑phase studies and conference abstracts:

• STELLA Phase 1/2a (NCT04657068): ART0380 combined with low‑dose irinotecan in advanced/metastatic solid tumors
• Confirmed ORR by RECIST at RP2D:
  • 45–50% in ATM‑negative tumors (depending on cohort definition in analyses reported).
  • 37% in the broader ATM‑deficient group (ATM‑low or ATM‑negative).

• Responses included two confirmed complete responses in heavily pretreated pancreatic cancer; partial responses were observed in pancreatic, colorectal, and several other tumor types. Median DOR/PFS were not mature in the abstracted dataset. (aacrjournals.org)

• Monotherapy (Phase 1/1b, part of NCT04657068): Initial ESMO 2023 readout reported tumor shrinkage and “durable confirmed responses” in selected, high‑replication‑stress cancers (e.g., high‑grade endometrial cancer) in a biomarker‑enriched cohort. Quantitative response rates were not detailed in the press release. (artios.com)

No peer‑reviewed, full manuscripts of clinical outcomes were identified as of October 2025; results are from conference abstracts and sponsor communications.

Safety

• Combination with low‑dose irinotecan: The AACR 2025 clinical abstract reported the regimen was “well tolerated and suitable for long‑term dosing,” without listing high‑grade event frequencies in the abstract text. (aacrjournals.org)
• Monotherapy: The ESMO 2023 communication described a predictable, manageable, reversible on‑target anemia; overall safety was considered tolerable with both intermittent and continuous dosing. Detailed grade ≥3 AE rates were not provided in the release. (artios.com)

Overall, the emerging profile is consistent with ATR class effects (myelosuppression—especially anemia—and gastrointestinal AEs), but precise incidence data for ART0380 await full publication.

Ongoing and recent trials

• NCT04657068 (STELLA): Phase 1/2a dose‑escalation/expansion of ART0380 as monotherapy and in combination with gemcitabine or irinotecan in advanced solid tumors; multiple US/EU sites. Estimated completion December 2026. (fdaaa.trialstracker.net)
• NCT05798611 (ARTIST): Phase 2 basket study of ART0380 monotherapy in biologically selected tumors (including endometrial cancer). The public trial registries/trackers list status updates through mid‑2025; no results posted. (cdek.pharmacy.purdue.edu)
• A randomized Phase 2 cohort in platinum‑resistant ovarian cancer testing ART0380 plus gemcitabine was initiated in 2023; initial data were planned for 1H 2025. Peer‑reviewed outcomes have not been identified yet. (artios.com)

Further reading

• Discovery/chemistry of ART0380 (Journal of Medicinal Chemistry, 2024). (pubs.acs.org)
• AACR 2025 clinical abstract (ART0380 + low‑dose irinotecan; late‑breaking, oral). (aacrjournals.org)
• AACR 2025 preclinical poster (ART0380 + irinotecan synergy in ATM‑negative models). (aacrjournals.org)
• Sponsor summaries: STELLA trial AACR 2025 update; ESMO 2023 monotherapy update; program overview. (artios.com)

Notes and limitations

• Publicly available clinical data are currently limited to conference abstracts and sponsor press releases; comprehensive peer‑reviewed clinical publications (e.g., full Phase 1/2a manuscripts with detailed safety tables) were not found as of October 7, 2025. (aacrjournals.org)

Last updated: Oct 2025