Novel TROP2-Targeting ADC Gains FDA Orphan Drug Status in Cholangiocarcinoma

OBI-902, a novel TROP2-targeting antibody-drug conjugate (ADC), has been awarded FDA orphan drug designation in cholangiocarcinoma.¹

Orphan drug status is awarded to novel agents intended to prevent, diagnose, or treat rare diseases or conditions.² Cholangiocarcinoma, a set of rare malignancies in the biliary tract, accounts for only 3% of gastrointestinal cancers and carries a 5-year survival rate of 20% or less, necessitating development of novel therapeutics to overcome the disease’s lack of approved treatments and poor prognosis.³

With sponsors of designated drugs qualifying for user fee exemptions, tax credits for clinical trials, and a potential 7 years of market exclusivity after approval, this designation marks another promising step forward in OBI-902’s development pathway following the April 2025 FDA clearance of OBI-902’s investigational new drug application.⁴

"Based on our preclinical data, OBI-902 has several important advantages over other TROP2 ADCs either approved or in development; including high stability in blood circulation, excellent bystander effect that extends the killing to neighboring cancer cells lacking TROP2 expression, potential ability to overcome drug resistance, and outstanding activity in animal and organoid models of cancer,” said Heidi Wang, PhD, CEO of OBI Pharma, in a news release.¹ “Importantly, this marks the first time an ADC that incorporates OBI's proprietary GlycOBI^® ADC technology is being evaluated in patients, including those diagnosed with cholangiocarcinoma. We look forward to investigating this potential best-in-class TROP2 ADC in the clinic."

An open-label phase 1/2 clinical trial of OBI-902 (NCT07124117) is underway and actively recruiting patients in sites across the US and Taiwan.⁵ The study aims to enroll a total of 111 adult patients with advanced or metastatic solid tumors not curable with local therapies and who have received established standard-of-care treatment.

The trial consists of dose-escalation and dose-expansion stages. The study first aims to establish the maximum tolerated dose of OBI-902 as monotherapy in various cohorts at escalating dose levels of 1.6 mg/kg, 3.0 mg/kg, 4.5 mg/kg, 6.0 mg/kg, 8.0 mg/kg, and 10.0 mg/kg administered every 3 weeks. In the expansion phase, the study will further explore the safety and preliminary activity of OBI-902 at the determined recommended phase 2 dose.

Mechanistic Rationale for OBI-902

OBI-902 is a site-specific glycan-based ADC consisting of an anti-TROP2 monoclonal antibody linked to a topoisomerase I inhibitor payload. With improved linker-payload stability and enhanced hydrophilicity from OBI Pharma’s proprietary GlycOBI^® platform, the agent is designed to deliver a potent topoisomerase I inhibitor payload to tumor cells expressing the TROP2 protein.

Preclinical data presented at the 2025 American Association for Cancer Research (AACR) meeting indicated OBI-902’s favorable pharmacokinetic profile and durable antitumor activity in xenograft models of non–small cell lung cancer, pancreatic cancer, gastric cancer, and colorectal cancer, where TROP2 is often overexpressed.⁶ Specifically, in gastric cancer models, OBI-902 achieved a 3.2- to 6.2-fold improvement in tumor volume reduction compared with the benchmark ADC, datopotamab deruxtecan (Dato-DXd; Datroway).

REFERENCES

1. OBI-902 has been granted by US FDA for orphan drug designation for the treatment of cholangiocarcinoma. News release. OBI Pharma. November 17, 2025. Accessed November 17, 2025. https://tinyurl.com/3b9wnw5r

2. Designating an orphan product: drugs and biological products. US Food & Drug Administration. Updated August 12, 2024. Accessed November 17, 2025. https://tinyurl.com/5n77pu2w

3. Qurashi M, Vithayathil M, Khan SA. Epidemiology of cholangiocarcinoma. Eur J Surg Oncol. 2025;51(2):107064. doi:10.1016/j.ejso.2023.107064

4. OBI Pharma announces U.S. FDA clearance of IND application for a phase 1/2 study of OBI-902, a Trop-2 targeting ADC. News release. OBI Pharma. May 1, 2025. Accessed November 17, 2025. https://tinyurl.com/4p7pk9fs

5. A study evaluating OBI-902 in participants with advanced solid tumors. ClinicalTrials.gov. Updated August 29, 2025. Accessed November 17, 2025. https://clinicaltrials.gov/study/NCT07124117

6. Hsu RY, Lu CH, Shia CS, et al. OBI-902, a novel TROP2 targeted antibody-drug conjugate via GlycOBI platform, has favorable pharmacokinetics and sustained antitumor activities in challenging solid tumors. Presented at American Association for Cancer Research Annual Meeting; April 25-30, 2025; Chicago, IL. Abstract 4356/21.