FDA Approves Orphan Drug Status for ADRX-0405 in Gastric Cancer

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to ADRX-0405, a promising therapeutic agent developed by Adcentrx Therapeutics, for the treatment of gastric cancer. This designation marks a significant milestone for the company and highlights the potential of ADRX-0405 to address unmet medical needs in a patient population facing dire prognoses due to advanced gastric malignancies.

ADRX-0405 is an antibody-drug conjugate (ADC) that specifically targets the six-transmembrane epithelial antigen of the prostate 1 (STEAP1), a cell surface protein that is frequently overexpressed in various malignancies, particularly prostate and gastric cancers. The drug employs a novel topoisomerase inhibitor as a linker payload, enhancing its delivery and efficacy against tumor cells. This innovative approach aims to improve therapeutic outcomes for patients suffering from advanced solid tumors, including gastric cancer, metastatic castration-resistant prostate cancer (mCRPC), and non-small cell lung cancer (NSCLC).

According to Hui Li, PhD, founder and CEO of Adcentrx Therapeutics, “Receiving orphan drug designation from the FDA is a notable milestone for Adcentrx and reinforces the potential for ADRX-0405 to improve the lives of patients with gastric cancer.” The company is currently conducting a phase 1a/b clinical trial (NCT06710379) to evaluate the safety, tolerability, pharmacokinetics, and optimal dosing regimen of ADRX-0405. The trial aims to enroll patients with measurable disease as per the RECIST 1.1 criteria, ensuring that only those with confirmed diagnoses participate in the study.

Preclinical studies have demonstrated promising results for ADRX-0405, reporting an impressive 83% overall response rate in prostate cancer models, which suggests potential efficacy in treating gastric cancer as well. The primary endpoint of the trial is to assess the incidence of adverse effects, while secondary endpoints include evaluating pharmacokinetic measures, overall response rate, duration of response, disease control rate, progression-free survival, and overall survival.

The phase 1a portion of the trial will involve dose escalation to ascertain the maximum tolerated dose and the recommended dose for expansion. Enrollment criteria necessitate that patients exhibit adequate hematologic, liver, and renal function, and they must not have active or uncontrolled central nervous system metastases, significant cardiovascular disease, or a history of another malignancy within the last three years.

As of January 2025, Adcentrx Therapeutics announced that the first patient had been dosed in the trial, with the first data readout anticipated in the fourth quarter of 2025. The implications of this designation and ongoing clinical investigation extend beyond gastric cancer, as the potential success of ADRX-0405 may pave the way for novel ADCs targeting STEAP1 in other malignancies as well.

The orphan drug designation not only facilitates accelerated development and review processes but also provides Adcentrx Therapeutics with various financial incentives, including tax credits for clinical trial costs and potential market exclusivity for seven years upon approval. This designation is particularly critical given the high mortality rates associated with gastric cancer, which continues to represent a significant challenge in oncology.

In summary, the FDA's orphan drug designation for ADRX-0405 underscores the urgent need for effective treatments for gastric cancer and exemplifies the innovative research conducted by Adcentrx Therapeutics in the field of targeted cancer therapies. The outcome of the ongoing phase 1a/b trial will be pivotal in determining the future clinical utility of ADRX-0405 for patients battling this challenging disease.