Aprea Therapeutics, Inc. (NASDAQ: APRE) has announced the initiation of twice-daily (BID) dosing of ATRN-119 in its ABOYA-119 Phase 1/2a clinical trial. This strategic shift aims to optimize clinical outcomes for patients with advanced solid tumors harboring DNA damage response (DDR) gene mutations. The trial, designed to evaluate ATRN-119 as a monotherapy, has begun dosing patients at 550 mg twice daily, a total daily dose of 1,100 mg.
Rationale for Twice-Daily Dosing
The decision to implement twice-daily dosing is rooted in scientific evidence suggesting that more frequent administration of ATRN-119 can sustain optimal therapeutic levels over a 24-hour period. This approach is intended to enhance the drug's efficacy by providing better target coverage and maximizing clinical benefit. According to Aprea, this dosing regimen could potentially accelerate the path to regulatory approval and commercialization.
ABOYA-119 Trial Design
The ABOYA-119 trial is a Phase 1/2a study evaluating ATRN-119 as a monotherapy in patients with advanced solid tumors who have at least one mutation in a defined panel of DDR-related genes. The trial initially tested once-daily doses ranging from 50 to 800 mg. With the protocol amendment, the trial will now independently study both once-daily and twice-daily dosing schedules.
The primary endpoint of the trial is to assess the tolerability and pharmacokinetics of ATRN-119. Aprea anticipates a Phase 1 readout in the second half of 2025.
Expert Commentary
Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea, stated, “Twice daily dosing represents a proactive step to de-risk the trial, potentially increasing the probability of success...we believe it positions the ATRN-119 program as a high-value asset that may be differentiated from other ATR inhibitors. To our knowledge, we believe ATRN-119 is the only ATR inhibitor in clinical development that is currently being tested as monotherapy on a continuous twice daily schedule.”
Anthony Tolcher, M.D., CEO of NEXT Oncology and an investigator in the ABOYA-119 trial, added, “Inhibition of ATR has emerged as a promising strategy for cancer treatment that exploits synthetic lethal interactions with proteins that are involved in DNA damage repair. This mechanism holds considerable promise for patients with difficult-to-treat cancers...a twice daily dosing regimen of ATRN-119 may allow us to maximize the therapeutic potential of the drug.”
About ATRN-119
ATRN-119 is a first-in-class macrocyclic ATR inhibitor designed for patients with mutations in DDR-related genes. These cancers represent a high unmet medical need, as patients with DDR-related gene mutations often have a poor prognosis and limited effective therapies available.
Aprea's Broader Strategy
Aprea Therapeutics is focused on developing therapies that exploit cancer cell mutations to selectively kill tumors while minimizing harm to healthy cells. Their pipeline includes APR-1051, an oral WEE1 kinase inhibitor, and ATRN-119, both in clinical development for solid tumor indications.
