FDA Grants Orphan Drug Designation to FF-10832 for Biliary Tract Cancer

FDA

The FDA has granted orphan drug designation to FF-10832—an investigational liposomal formulation of gemcitabine—for the treatment of patients with biliary tract cancer.1

“Biliary tract cancers are rare but aggressive malignancies associated with a poor prognosis and limited treatment options,” Susumu Shimoyama, president of FUJIFILM Pharmaceuticals U.S.A., stated in a news release. “Receiving orphan drug designation highlights the significant unmet medical need that still remains and supports [the] development of FF-10832 for patients with biliary tract cancer who have few satisfactory options.”

Data from the biliary tract cancer expansion cohort (n = 18) of a first-in-human dose-findings trial (NCT03440450) investigating FF-10832 in patients with solid tumors were presented at the 2025 ASCO Annual Meeting.2 This cohort enrolled patients at least 18 years of age with metastatic or unresectable cholangiocarcinoma or gallbladder cancer whose disease had progressed on gemcitabine plus cisplatin or gemcitabine-based therapy; had received a maximum of 3 prior lines of systemic therapy; had evaluable disease per RECIST 1.1 criteria; had an ECOG performance status of 0 or 1; and had a life expectancy of at least 3 months. Patients in this cohort were treated with FF-10832 at the recommended phase 2 dose of 40 mg/m2 on day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Among the 18 treated patients, the median dose intensity was 90.6% (95% CI, 62.5%-100%), and patients received a median of 3.5 cycles (range, 1-28). The 2 patients who remained on study for 9.2 months (12 cycles) and 23.3 months (28 cycles) required dose reduction to 23 mg/m2 by cycles 3 and 21, respectively, due to fatigue. Three patients required dose interruptions due to infusion-related reactions (IRRs) at cycle 1; all dosing in these patients was completed.

The most common any-grade treatment-related adverse effects (TRAEs) were decreased appetite (44.4%), nausea (38.9%), pyrexia (38.9%), fatigue (33.3%), vomiting (33.3%), headache (27.8%), muscular weakness (27.8%), thrombocytopenia (27.8%), dehydration (22.2%), anemia (16.7%), back pain (16.7%), chills (16.7%), influenza-like illness (16.7%), and IRR (16.7%). The most common grade 3 TRAEs were muscular weakness (16.7%), thrombocytopenia (11.1%), anemia (11.1%), pyrexia (5.6%), fatigue (5.6%), musculoskeletal pain and back pain (5.6%), hyperbilirubinemia (5.6%), and hypernatremia (5.6%). No grade 4 or higher TRAEs were reported.

The overall response rate among efficacy-evaluable patients (n = 16) was 12.5%; the 2 responders achieved partial response (PR). Best responses of stable disease (SD) and progressive disease (PD) occurred in 9 and 4 of patients, respectively. One patient was not evaluable for response. Additionally, prolonged disease control was observed in 4 patients, 2 of whom remained on the study at data cutoff.

Best radiographic responses by tumor type included PR (perhilar cholangiocarcinoma, n = 1; gallbladder cancer, n = 1), SD (intrahepatic cholangiocarcinoma, n = 7; distal cholangiocarcinoma, n = 1; perhilar cholangiocarcinoma, n = 1), and PD (perhilar cholangiocarcinoma, n = 1; intrahepatic cholangiocarcinoma, n = 3).

In total, 16 patients discontinued treatment due to disease progression (n = 11), patient decision (n = 2), withdrawal of consent (n = 1), sepsis or respiratory failure (n = 1), and pursual of hospice (n = 1). The median time on study was 18 weeks (range, 3.3-169.1).

The median progression-free survival was 2.8 months (95% CI, 1.3-6.7), and the median overall survival was 9.1 months (95% CI, 5.6-not reached).

Released gemcitabine from FF-10832 induced an antitumor microenvironment that featured decreased levels of CD4-positive Tregs and M2 macrophages, as well as increased levels of antitumor CD8-positive T cells and M1 macrophages. These reports are consistent with previously reported antitumor immune activation in the tumor microenvironment with gemcitabine.

Notably, FF-10832 is also currently under investigation as monotherapy and in combination with pembrolizumab (Keytruda) for the treatment of patients with solid tumors, including urothelial cancer and non–small cell lung cancer, in a phase 2a trial (NCT05318573).3

References

1. FF-10832 granted FDA orphan drug designation for the treatment of biliary tract cancer. News release. FUJIFILM Pharmaceuticals U.S.A., Inc. July 7, 2025. Accessed July 8, 2025. https://www.fujifilm.com/us/en/news/ff-10832-granted-fda-orphan-drug-designation-for-the-treatment-of-biliary-tract-cancer
2. Falchook GS, Borazanci EH, Lin BS, et al. Phase 1 expansion study of FF-10832 (liposomal gemcitabine) antitumor activity in patients with advanced biliary carcinomas. J Clin Oncol. 2025;43(suppl 16):4092. doi: 10.1200/JCO.2025.43.16_suppl.4092
3. A study to evaluate safety, efficacy of FF-10832 in combo with pembrolizumab in urothelial & non-small cell lung cancer. ClinicalTrials.gov. Updated April 10, 2025. Accessed July 8, 2025. https://clinicaltrials.gov/study/NCT05318573