On April 29, 2025 Artios Pharma Limited ("Artios"), a clinical-stage biotech company led by pioneers of DNA damage response ("DDR") drug development, reported encouraging data from its ongoing STELLA Phase 1/2a trial (NCT04657068) in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago (Press release, Artios Pharma, APR 29, 2025, View Source [SID1234652301]). The presentation by Principal Investigator Susanna Ulahannan, MD, Associate Professor, Stephenson Cancer Center at the University of Oklahoma and Director, Drug Development, Sarah Cannon Research Institute (SCRI) at OU Health Stephenson Cancer Center, highlighted the Phase 1/2a clinical data from the STELLA trial of Artios’ lead candidate, ART0380, in combination with low-dose irinotecan in advanced or metastatic solid tumors.
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Artios is pursuing a differentiated clinical development path with its lead product candidate, ART0380, which selectively targets a protein kinase called Ataxia telangiectasia and Rad3-related (ATR). ATR plays a key role in the cellular response to replication stress, a process that can occur endogenously or exogenously, for example via chemotherapy. Many cancers exhibit high endogenous replication stress, such as Ataxia-Telangiectasia Mutated (ATM) protein deficiency found in up to 24% of high-unmet need solid tumors. Artios’ innovative approach exploits replication stress to kill cancer cells through triple targeting: selecting cancers with high replication stress, inducing further replication stress with a low dose of irinotecan, and preventing cellular rescue by inhibiting ATR with ART0380.
"Artios is exploiting a new area of DNA damage response called replication stress with ART0380, and the data from our Phase 1/2a study shows robust clinical activity and good tolerability in a large, identifiable patient population," said Ian Smith, Chief Medical Officer of Artios. "These are unprecedented data for the ATR inhibitor class, and they validate our unique approach of combining ART0380 with a low dose of irinotecan to amplify replication stress. We are encouraged by the incidence and durability of the responses in ATM-deficient cancers, including those of particularly high unmet need, such as pancreatic and colorectal cancer."
Summary of Key Clinical Results:
Artios completed patient enrollment in the dose escalation and initial expansion. As of the data cut-off in February 2025, 87 patients with advanced/metastatic solid tumors who had no satisfactory alternative therapy available to them were treated with ART0380 in combination with low-dose irinotecan, of which 58 patients were treated at the RP2D (recommended Phase 2 dose). These patients’ tumors had varying levels of ATM protein.
The combination treatment at the RP2D showed a meaningful duration of response and prolonged clinical benefit across multiple histologies
37% confirmed overall response rate (cORR) in patients with ATM-negative1 and ATM-low1 cancers (14/38), according to RECIST
50% cORR in ATM-negative cancers (10/20) with a median duration of response (mDoR) of 5.7 months (several responses ongoing)
22% cORR in ATM-low cancers (4/18) with the median duration of response not reached
Responses were observed in 8 different solid tumor types
The combination had a favorable safety profile, was well tolerated, and was shown to be suitable for long-term dosing
The 21-day combination treatment regimen at the RP2D includes administering ART0380 (200mg) on days 1 – 3 and 8 – 10, and irinotecan (60mg/m²) on days 1 and 8.
"The first results from the ongoing STELLA clinical trial are compelling and demonstrate the potential for ART0380-irinotecan combination treatment in ATM biomarker-driven tumors. I am encouraged by the clinical activity and durable responses across multiple cancer indications in heavily pretreated patients, especially considering the complete responses observed in metastatic pancreatic cancer," added Susanna Ulahannan, MD, Director, Drug Development, SCRI at OU Health Stephenson Cancer Center, USA.
The Phase 1/2a trial for ART0380 is conducted with SCRI’s contract research organization, SCRI Development Innovations. Based on the meaningful clinical responses observed, Artios is initiating expansion studies in earlier-line settings, including colorectal and pancreatic cancers, to enable pivotal development of ART0380.
About ART0380
ART0380 is an orally administered, selective small molecule inhibitor of ataxia telangiectasia and Rad3-related protein (ATR) with first- and best-in-class potential. ATR is activated as the cell’s response to replication stress frequently occurring in rapidly multiplying cells. Inhibiting ATR with ART0380 removes a cancer cell’s ability to repair damaged DNA, leading to the killing of cancerous cells. ART0380 is designed to maximize the therapeutic window and is optimized for combination with DNA damaging therapy to improve patient outcomes. It is currently being evaluated in multiple clinical settings to identify its potential in high replication stress tumors. ART0380 was originally in-licensed by Artios from The University of Texas MD Anderson Cancer Center and ShangPharma Innovation in 2019. The molecule was discovered as part of a collaboration between ShangPharma and MD Anderson’s Therapeutics Discovery Division.