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

The liposomal formulation of gemcitabine may enhance anti-tumor activity by increasing plasma half-life and improving targeted delivery to tumors.

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, according to a press release from the developer, Fujifilm.¹

The developers noted that using the agent for intravenous administration is designed to enhance anti-tumor activity by prolonging plasma half-life and improving targeted delivery to tumors.

According to the company’s website, liposomal encapsulation of gemcitabine enhances its combined effect with CTLA-4 immune checkpoint inhibitors via high API accumulation in tumor tissue through the enhanced permeability and retention effect, an increase in M1 macrophages and CD8-positive T cells, and a decrease in M2 macrophages in the tumor microenvironment.²

Currently, FF-10832 is being investigated in a phase 2a trial (NCT05318573) designed to evaluate the safety and efficacy of the agent as monotherapy and in combination with pembrolizumab (Keytruda) in the treatment of patients with solid tumors.

Previously, FF-10832 was evaluated in a dose-escalation phase 1 study (NCT03440450) that evaluated the safety profile and dosage of the agent in the treatment of those with advanced solid tumors including biliary tract cancer.

“[Biliary tract cancers] are rare but aggressive malignancies associated with a poor prognosis and limited treatment options,” stated Susumu Shimoyama, president of Pharmaceuticals USA, Inc., in the press release.¹ “Receiving orphan drug designation highlights the significant unmet medical need that still remains and supports development of FF-10832 for patients with [biliary tract cancer] who have few satisfactory options.”

Phase 1 Trial

The phase 1 trial enrolled a total of 90 patients.³ Those who were eligible were 18 years or older with histologically or cytologically confirmed metastatic solid tumors; relapsed or refractory to standard therapy; and at least 3 weeks beyond their last chemotherapy, radiotherapy, major surgery, or experimental treatment. Additionally, patients had an ECOG performance of 1 or less and a life expectancy of at least 3 months.

In the biliary tract cancer cohort expansion phase, patients had histologically or cytologically confirmed cholangiocarcinoma or gallbladder carcinoma that was metastatic pancreatic adenocarcinoma following progression or relapse; measurable disease per RECIST v1.1 criteria; progressed on at least 1 prior line of gemcitabine/cisplatin or gemcitabine-based therapy; and had not received more than 3 prior systemic therapies for their tumor.

Exclusion criteria included not receiving standard therapies expected to improve survival by at least 3 months; prior hypersensitivity to gemcitabine; any active infection requiring intravenous antibiotic usage within the last week prior to study treatment; and HIV, hepatitis B virus surface antigen, or hepatitis C virus.

In all cohorts, FF-10832 was diluted in dextrose 5% in water and intravenously infused continuously over 30 to 120 minutes, and FF-10832 was administered on days 1 and 15 of each 28-day cycle. In cohorts 1, 2, 3, and 4, FF-10832 was administered at 1.2 mg/m², 2.4 mg/m², 4.8 mg/m², and 8 mg/m², respectively. In the expansion cohort, treatment was given at the recommended phase 2 dose (RP2D); it was specified that, for patients with biliary tract cancer, FF-10832 was given at the RP2D on day 1 of each 21-day cycle.

The trial’s primary end points were the incidence of treatment-emergent adverse events (TEAEs), dose-limiting toxicities, and maximum tolerated dose. Secondary end points were disease assessment by CT or MRI, duration of response, duration of stable disease, time to progression, progression-free survival, and overall survival.

Phase 2a Trial

This trial has an estimated enrollment of 120 patients with an estimated study completion date of November 2029.⁴

Eligible patients are 18 years or older with histologically or cytologically confirmed advanced or metastatic solid tumors who have disease progression after treatment with standard therapies for metastatic disease known to confer benefit, or are intolerant to treatment. Patients also have measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and a life expectancy of at least 3 months. In the expansion phase, patients were required to have urothelial cancer or non–small cell lung cancer and have progression on prior anti–PD-(L)1 therapy.

Patients are excluded if they receive prior systemic anti-cancer therapy within 4 weeks of treatment, receive prior radiotherapy within 2 weeks of starting study treatment, receive a live or live-attenuated vaccine within 30 days of the first study dose, and have an allogeneic tissue or solid organ transplant.

FF-10832 will be administered at 40 mg/m² in all cohorts on day 1 of each 21-day cycle, and pembrolizumab will be administered at 200 mg.

The trial’s primary end points are the incidence of TEAEs, duration of stable disease with FF-10832 monotherapy, and duration of stable disease with combination therapy. Secondary end points include safety, overall response rate, duration of response, progression-free survival, and overall survival.

References

1. FF-10832 granted FDA orphan drug designation for the treatment of biliary tract cancer. News release. Fujifilm Pharmaceuticals USA. July 7, 2025. Accessed July 8, 2025. https://tinyurl.com/bdza5hee
2. Liposomes. Fujifilm. Accessed July 8, 2025. https://tinyurl.com/ycycvayd
3. A phase 1 dose-escalation study of FF-10832 for treatment of solid tumors including biliary tract cancer. ClinicalTrials.gov. Updated May 18, 2025. Accessed July 8, 2025. https://tinyurl.com/5c4krbrw
4. 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://tinyurl.com/38hy3njw