FDA Grants Fast Track to Alnodesertib Combo for Metastatic Colorectal Cancer

The FDA has granted fast track designation to the combination of alnodesertib (formerly ART0380) and irinotecan for the treatment of ATM-negative metastatic colorectal cancer (mCRC).^1,2

The designation is supported by interim positive data from the ongoing phase 1/2a STELLA trial (NCT04657068) presented earlier this year at the 2025 American Association for Cancer Research Annual Meeting. Here, the combination was determined to be well-tolerated by patients with advanced solid tumors in the third line, with the most frequently reported treatment-related adverse events being neutropenia (53%), anemia (41%), fatigue (33%), and diarrhea (31%).³

The data also revealed encouraging preliminary efficacy among the 87 patients dosed so far with the combination. Among patients with ATM-negative CRC and other solid tumors, the confirmed objective response rate (ORR) per RECIST was 45%, with a median duration of response (DOR) of 5.2 months (range, 1.4–10.7). These figures compare favorably with those whose tumors expressed the ATM protein (ORR, 0%; median DOR, not applicable).

“Patients with third-line [CRC] face a dismal prognosis, with current standards of care for third-line mCRC delivering response rates in the single digits. In our studies to date, alnodesertib has demonstrated compelling clinical activity in ATM-negative patients with mCRC as well as in other heavily pretreated cancer types with high endogenous replication stress,” said Ian Smith, chief medical officer of Artios Pharma, in a news release.² “These results, together with activity across other solid tumors, highlight alnodesertib’s potential to deliver meaningful benefit where treatment options are limited. The FDA’s [f]ast [t]rack designation recognizes both the strength of our early clinical data and the urgent need for new therapies, while also providing the opportunity for enhanced interactions with the [a]gency.”

The FDA grants fast track status to agents intended to fill serious unmet medical needs.⁴ As the second leading cause of cancer-related deaths globally,⁵ CRC requires treatments that can significantly prolong patient survival. Despite recent advancements in therapy, many patients with mCRC eventually exhaust all available treatment options, highlighting a critical need for more effective treatments.⁶

The alnodesertib combination is designed to address this treatment gap through a triple-pronged approach. A low dose of irinotecan, a chemotherapy drug, damages tumor cell DNA, while alnodesertib, an oral selective small molecule inhibitor of the ATR protein, targets tumors to block DNA repair, resulting in an enhanced antitumor response.

“We consider this a triple hit because we target the cancer in [3] different ways. We target the right tumor (those with ATM deficiency) and then we attack it with [2] treatments that work synergistically, one that damages the DNA and the other that prevents the cancer cell from repairing the DNA and surviving,” said Susanna Ulahannan, MD, oncologist and associate professor in the University of Oklahoma College of Medicine and principal investigator for the STELLA CRC cohort, in another news release.¹ “The treatment responses we have seen are very exciting, and they are in a patient group that has very few options.”

The designation will enable expedited clinical development and regulatory review to ultimately deliver this combination to patients earlier.

About the STELLA Trial

The STELLA trial is an open-label phase 1/2a trial designed to evaluate the safety, tolerability, and preliminary efficacy of alnodesertib as monotherapy and combined with irinotecan or gemcitabine in advanced or metastatic solid tumors.⁷

The recommended phase 2 dose (RP2D) for the combination was established as 200 mg of alnodesertib on days 1 to 3 and 8 to 10, plus 60 mg/m² of irinotecan on days 1 and 8 of a 21-day cycle. Among the 58 patients who had received the RP2D as of November 1, 2024, the number of prior lines of therapy ranged from 1–7, and 59% had received prior irinotecan.³

Recruitment for the study is ongoing, with an estimated enrollment of 502 patients encompassing a broad range of tumor types including CRC, ovarian cancer, endometrial cancer, esophageal cancer, pancreatic cancers, and cholangiocarcinoma that fail to express ATM.

REFERENCES

1. FDA grants fast-track designation to drug combo for colorectal cancer. News release. The University of Oklahoma. November 10, 2025. Accessed November 12, 2025. https://tinyurl.com/mrmc5bx2

2. Artios receives U.S. FDA fast track designation for alnodesertib in ATM-negative metastatic colorectal cancer (mCRC). News release. Artios Pharma Limited. September 24, 2025. Accessed November 12, 2025. https://tinyurl.com/ucu27e9w

3. Ulahannan S, Henry JT, Moore KN, et al. First results of ART0390 (an ATR kinase inhibitor) with low dose irinotecan in advanced or metastatic solid tumors. Cancer Res. 2025;85(suppl 2):CT267. doi:10.1158/1538-7445.AM2025-CT267

4. Fast track. US Food & Drug Administration. Updated August 13, 2024. Accessed November 12, 2025. https://tinyurl.com/ms2695jn

5. Newcomer KL, Fenstermacher DA, Schmitt C. Understanding and addressing unmet needs in colorectal cancer: Findings from the Colorectal Cancer Alliance’s Patient and Survivor survey. J Clin Oncol. 2025;43(16_suppl):3576-3576. doi:10.1200/jco.2025.43.16_suppl.3576

6. Melosky B. Meeting an unmet need in metastatic colorectal carcinoma with regorafenib. Asia Pac J Oncol Nurs. 2016;3(1):58-65. doi:10.4103/2347-5625.178174

7. A study of ART0380 for the treatment of advanced or metastatic solid tumors. ClinicalTrials.gov. Updated October 14, 2025. Accessed November 12, 2025. https://www.clinicaltrials.gov/study/NCT04657068