FDA Clears IND Application for TROP-2 Targeting ADC in Solid Tumors

Investigators are planning to begin enrollment for a phase 1/2 trial throughout the second half of 2025.

The FDA has cleared an investigational new drug (IND) application for the TROP-2 targeted antibody drug conjugate (ADC), OBI-902, to conduct a phase 1/2 study in patients with solid tumors, according to a news release from the drug’s developers OBI Pharma, Inc.1

Support for the decision came from preclinical data presented at the 2025 American Association for Cancer Research Annual Meeting, which evaluated OBI-902 across challenging mouse tumor models compared with benchmarks.2 Therein, OBI-902 conjugated via site-specific glycan linkers, maintaining a homogenous drug-to-antibody ratio in serum albumin, which in turn, offered enhanced stability.

Additional findings from the trial revealed that OBI-902 elicited a favorable pharmacokinetic profile, with the total antibody achieving a maximum serum concentration (Cmax) of 45 ± 1.7 µg/mL, an area under the curve (AUC) of 4400 ± 230 µg/mL, and a half-life of 91 hours. Furthermore, the tumor-free payload of OBI-902 at 3 mg/kg elicited a higher Cmax of 3.6 ± 0.30 ng/g than its benchmark comparators; 3 mg/kg of sacituzumab tirumotecan (Sac-TMT) elicited a Cmax of 2.6 ± 0.23 ng/g, and 10 mg/kg of datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) elicited a Cmax of 3.1 ± 0.44 ng/g. The respective AUCs were 960 ± 37 hours*ng/g, 230 ± 26 hours*ng/g, and 480 ± 32 hours*ng/g with OBI-902, sac-TMT, and Dato-DXd. Investigators noted that the results for the hours was obtained from a separate experiment.

“The impending OBI-902-001 clinical trial intends to evaluate the safety, pharmacokinetics, and preliminary efficacy of OBI-902 in patients with advanced solid tumors. We are very excited to begin dosing patients in our phase 1/2 clinical study of OBI-902 later this year,” Heidi Wang, chief executive officer of OBI Pharma, said in the news release on the FDA decision.1

The preclinical study was conducted to improve the ADC stability and enhance payload delivery to TROP-2 overexpressing tumors, which correlate with poor prognoses. Contextualized by this need, the study aimed to provide preclinical evidence showing an enhanced linker-payload stability, efficient tumor-targeted payload delivery, and superior antitumor activity in challenging mouse tumor models.

The study end points included the in vitro stability of OBI-902’s payload assessed after 14-day incubation with human serum albumin, 21-day pharmacokinetics of OBI-902 evaluated in a human non–small cell lung cancer (NSCLC) xenograft model following intravenous dosing, the biodistribution of 111In-DTPA-OBI-902 in a human NSCLC xenograft model, the bystander killing effect of OBI-902 assessed in NCI-H460-luciferase cells cultured alone or with BxPC-3 cells, and antitumor activity.

Additional data from the trial revealed that OBI-902 exhibited time-dependent tumor uptake, achieving high tumor-to-blood ratios at later time points, including as late as 168 hours. Furthermore, in gastric cancer, the tumor volume reductions of OBI-902 were 3.6 to 6.2 times better by day 57 compared with benchmarks. In colorectal cancer, OBI-902 obtained a sustained tumor suppression by day 56 of 330 ± 110 mm3 vs benchmarks exceeding 1000 mm3 prior to day 18.

Survival data showed that OBI-902 demonstrated superior antitumor activity to benchmarks in large tumor CDX models. In a model evaluating pancreatic cancer outcomes, OBI-902 showed survival of more than 50 days vs 28 days in benchmark groups. In the NSCLC model, 40% of mice survived beyond day 70 with OBI-902 vs all benchmark-treated mice experiencing a tumor volume of greater than 1500 mm3 between days 29 and 42.

“OBI-902 efficiently delivers and slowly releases its payload to the tumor, achieving desirable drug exposure and sustained antitumor activity across various challenging solid tumors, suggesting its potential as a best-in-class TROP2 ADC,” Ren-Yu Hsu, senior scientist and analytical chemist at OBI Pharma, concluded in the presentation with study coinvestigators.2

Investigators are planning to begin enrollment for the phase 1/2 trial throughout the second half of 2025.

References

1. OBI Pharma announces U.S. FDA clearance of IND application for a phase 1/2 study of OBI-902, a Trop-2 targeting ADC. May 1, 2025. Accessed May 2, 2025. https://tinyurl.com/yc45mh2b
2. Hsu R-Y, Lu C-H, Shia C-S, 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 the 2025 American Association for Cancer Research Annual Meeting; April 25-30, 2025; Chicago, IL. Abstract 4356.