FDA Grants Orphan Drug Status to STEAP1-Targeting ADC for Gastric Cancer

The FDA has granted orphan drug designation to ADRX-0405, an investigational antibody-drug conjugate (ADC) being developed by Adcentrx Therapeutics, for the treatment of gastric cancer.¹ The compound is currently being evaluated in a phase 1a/1b clinical trial (NCT06710379) for advanced solid tumors.

This designation provides regulatory and financial incentives, including eligibility for 7 years of market exclusivity following approval, tax credits for clinical trial costs, exemption from certain FDA fees, and access to FDA guidance on clinical study design. These incentives aim to encourage the development of therapies for rare diseases, defined as conditions affecting fewer than 200,000 people in the US.

“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,” said Hui Li, PhD, founder and chief executive officer of Adcentrx, in a press 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.”

The ongoing phase 1a portion of the study is assessing the safety, tolerability, and preliminary efficacy of ADRX-0405 in several advanced solid tumors, including metastatic castration-resistant prostate cancer (mCRPC), non–small cell lung cancer, and gastric cancer.³ In phase 1a, increasing doses of ADRX-0405 will be administered to identify the maximum tolerated dose. Phase 1b will focus on treating patients with mCRPC.

Eight sites in California, Michigan, Minnesota, Texas, Utah, and Virginia are recruiting. For enrollment in part 1a, patients must have measurable disease according to RECIST v1.1, an ECOG performance status of 0 to 1, and adequate hematologic, liver, and renal function. Those with active and uncontrolled central nervous system metastases, significant cardiovascular disease, or a history of another malignancy within the past 3 years are not eligible for enrollment.

About Gastric Cancer and ADRX-0405

Gastric cancer, often diagnosed at advanced stages, remains a major clinical challenge due to limited effective treatment options in the refractory setting. Approximately 30,300 new cases of gastric cancer are expected in the US in 2025.²

ADRX-0405 is a STEAP1-targeted ADC that uses Adcentrx’s proprietary i-Conjugation® platform and combines a humanized IgG1 monoclonal antibody with a novel cleavable linker and a topoisomerase inhibitor payload. The drug-antibody ratio of 8 is designed to enhance cytotoxic payload delivery specifically to STEAP1-expressing tumor cells while minimizing off-target toxicity. Preclinical models have shown promising pharmacokinetics, a favorable safety profile, and antitumor activity across multiple solid tumor types, though clinical validation remains ongoing.

ADCs have gained increasing attention in recent years for their ability to selectively deliver cytotoxic agents to cancer cells. Several ADCs have received FDA approval in hematologic and solid tumors, but challenges remain, including optimizing stability, toxicity, and tumor penetration. ⁴ Adcentrx aims to address these challenges through its proprietary linker-payload chemistry.¹

REFERENCES:

1. U.S. FDA grants orphan drug designation to Adcentrx Therapeutics’ ADRX‑0405 STEAP1 ADC for gastric cancer. News release. July 8, 2025. Accessed July 9, 2025. https://tinyurl.com/yc7zh42t

2. Siegel RL, Kratzer TB, Giaquinto AN, et al. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10-45. doi:10.3322/caac.21871

3. A study of ADRX-0405 in subjects with select advanced solid tumors. ClinicalTrials.gov. Updated April 9, 2025. Accessed July 9, 2025. https://www.clinicaltrials.gov/study/NCT06710379

4. Beck A, Goetsch L, Dumontet C, Corvaïa N. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017;16(5):315-337. doi:10.1038/nrd.2016.268