Alnodesertib Wins FDA Fast Track Status in ATM-Negative Colorectal Cancer

The U.S. Food and Drug Administration (FDA) granted fast track designation to the ATR inhibitor alnodesertib plus low-dose irinotecan for the treatment of adult patients with ATM-negative metastatic colorectal cancer in the third-line setting, according to a news release from Artios.

“The fast track designation for alnodesertib underscores its first-in-class potential for third-line [metastatic colorectal cancer] patients with ATM-negative tumors,” Mike Andriole, CEO of Artios, said in the news release. “Approximately 3,000 patients with ATM-negative third-line [metastatic colorectal cancer] succumb to this disease annually in the U.S., with no treatment options that specifically address this protein deficiency. Alnodesertib has the potential to be the first treatment specifically for this invariably lethal disease. Additionally, we are encouraged by the durable responses this program has demonstrated across other tumor types, highlighting its ability to target replication stress across a range of solid tumors.”

Why Did the FDA Grant Fast Track Designation to Alnodesertib?

The designation was based on results from the ongoing phase 1/2a STELLA study, which is testing alnodesertib in combination with a low dose of irinotecan. In addition to benefits seen in third-line metastatic colorectal cancer, clinical responses were also observed in seven other solid tumor types with ATM deficiency. So far, the combination has shown a favorable safety profile, has been well tolerated, and appears suitable for long-term dosing.

“Patients with third-line colorectal cancer face a dismal prognosis, with current standards of care for third-line [metastatic colorectal cancer] delivering response rates in the single digits. In our studies to date, alnodesertib has demonstrated compelling clinical activity in ATM-negative patients with metastatic colorectal cancer as well as in other heavily pretreated cancer types with high endogenous replication stress,” Ian Smith, chief medical officer of Artios, said in the news release. “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 fast track 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 Agency.”

What is the FDA Fast Track dDsignation?

The FDA’s fast track program is meant to speed up the development and review of medicines that may meet urgent medical needs for serious or life-threatening conditions. Treatments with this designation may be eligible for priority review and accelerated approval if they meet the necessary requirements. This designation also allows the drug’s developer, Artios, to work more closely with the FDA as alnodesertib continues through clinical testing.

How Does Alnodesertib Work with Irinotecan?

Alnodesertib, previously known as ART0380, is a potential first-in-class oral drug that blocks a protein called ATR (ataxia-telangiectasia and Rad3-related protein). ATR plays a role in how cancer cells repair themselves. Artios’ approach combines alnodesertib with a low dose of the chemotherapy irinotecan, aiming to target cancers with high levels of replication stress, such as those with ATM protein deficiency.

Artios is advancing new strategies in what is called the DNA damage response field. This research focuses on stopping cancer cells from repairing damage to their DNA, which makes them more vulnerable to treatment. The company’s programs include alnodesertib, a Polθ (DNA polymerase theta) inhibitor called ART6043, and early-stage research such as DDRi-antibody-drug conjugates. The goal of these therapies is to block the survival pathways cancer cells depend on, with the hope of improving treatment outcomes for patients with difficult-to-treat cancers.

Reference

1. “Artios Receives U.S. FDA Fast Track Designation for alnodesertib in ATM-negative Metastatic Colorectal Cancer (mCRC).” Artios. News Release. Sep. 24, 2025.

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