FDA Grants Orphan Drug Designation to ADRX-0405 for Gastric Cancer

FDA

The FDA has granted orphan drug designation to ADRX-0405, a STEAP1-directed antibody-drug conjugate (ADC), for the treatment of patients with gastric cancer.1

The agent is under investigation in the phase 1a portion of an ongoing phase 1a/b trial (NCT06710379) in patients with certain advanced solid tumors, including metastatic castration-resistant prostate cancer (mCRPC), gastric cancer, and non–small cell lung cancer (NSCLC).

“Receiving orphan drug designation from FDA is a notable milestone for Adcentrx and reinforces the potential for ADRX-0405 to improve the lives of patients with gastric cancer,” Hui Li, PhD, founder and CEO of Adcentrx Therapeutics, stated in a news release. “We are encouraged by the progress of our phase 1a trial and look forward to further evaluating the safety, tolerability and antitumor activity of ADRX-0405 in gastric and other cancers.”

ADRX-0405 is a next-generation ADC targeting STEAP1, a cell surface protein that is upregulated primarily in prostate cancer and several other cancers, including gastric cancer. The ADC houses a humanized IgG1 antibody combined with a novel topoisomerase inhibitor linker payload to improve drug delivery. Specifically, ADRX-0405 binds STEAP1, which triggers H2AX phosphorylation and PARP cleavage, leading to nanomolar and target-dependent cytotoxicity in tumor cells.2

With a drug-antibody ratio of 8, ADRX-0405 has proved to be a highly stable ADC, showcasing favorable pharmacokinetics, safety, and efficacy in preclinical study.1,2 In a patient-derived xenograft mouse model of prostate cancer with high and low STEAP1 expression, ADRX-0405 led to an overall response rate (ORR) of 83%.2

The ongoing phase 1a/b trial was designed to evaluate the safety, tolerability, pharmacokinetics, and optimal dose of ADRX-0405 in patients with histologically confirmed mCRPC, gastric cancer, and NSCLC.3

To be eligible for enrollment, patients needed to have measurable disease according to RECIST 1.1 criteria or evaluable disease per Prostate Cancer Working Group 3 criteria for those with prostate cancer; an ECOG performance status of 0 or 1 in phase 1a or 0 to 2 in phase 1b; and adequate hematologic, liver, and renal function.

In phase 1b, patients must have histologically confirmed castration-resistant prostate adenocarcinoma with a serum testosterone level below 50 ng/dL that is intolerant or resistant to standard therapy.

Exclusion criteria include active and uncontrolled central nervous system metastases; significant cardiovascular disease; history of another malignancy within 3 years; exposure to any anticancer or investigational therapy within 5 elimination half-lives or 14 days, or 4 weeks for any therapeutic radiopharmaceutical for prostate cancer; history of interstitial lung disease or pneumonitis or a suspicion thereof, and exposure to systemic antimicrobial treatment for active infection.

In the phase 1a dose escalation portion of the trial eligible patients will receive escalating doses of ADRX-0405 to determine the maximum tolerated dose and recommended dose for expansion. In dose expansion only patients with previously treated mCRPC will receive ADRX-0405.

The primary end point is the incidence of adverse effects. Secondary end points include pharmacokinetic measures, as well as ORR, duration of response, disease control rate, progression-free survival (PFS), radiographic PFS, and overall survival.

In January 2025, the developer announced the first patient had been dosed in the trial. The first data readout is planned for the fourth quarter of 2025.4

References

1. U.S. FDA grants orphan drug designation to Adcentrx Therapeutics’ ADRX‑0405 STEAP1 ADC for gastric cancer. News release. Adcentrx Therapeutics. July 8, 2025. Accessed July 11, 2025. https://www.adcentrx.com/adcentrx-therapeutics-adrx-0405-steap-1-adc-granted-orphan-drug-designation-for-the-treatment-of-gastric-cancer/
2. Shahmoradgoli M, Hau AM, Betancourt O, et al. Preclinical characterization of a novel STEAP1 antibody-drug conjugate ADRX-0405 for the treatment of mCRPC. Cancer Res. 2025;85(suppl 8):1159. doi:10.1158/1538-7445.AM2025-1159
3. A study of ADRX-0405 in subjects with select advanced solid tumors. ClinicalTrials.gov. Updated April 9, 2025. Accessed July 11, 2025. https://clinicaltrials.gov/study/NCT06710379
4. Adcentrx Therapeutics announces first patient dosed in the phase 1a/b study of ADRX-0405, a potential first-in-class ADC targeting STEAP1 for the treatment of advanced solid tumors. News release. Adcentrx Therapeutics. January 6, 2025. Accessed July 11, 2025. https://www.adcentrx.com/adcentrx-therapeutics-doses-first-patient-in-phase-1a-with-adrx-0405-steap1-adc/