FDA Approves Futibatinib for FGFR2+ Cholangiocarcinoma

FDA

The FDA has granted an accelerated approval to futibatinib (Lytgobi) for adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions or other rearrangements.¹

The regulatory decision was supported by data from the multicenter, open-label, single-arm, phase 2 FOENIX*-CCA2 trial (TAS-120-101; NCT02052778), which showed that among 103 patients, futibatinib elicited an overall response rate (ORR) of 42% (95% CI, 32%-52%) by independent central review (ICR) and RECIST v1.1 criteria, with all responders experiencing partial responses.

The median duration of response (DOR) with the agent was 9.7 months (95% CI, 7.6-17.1). Seventy-two percent of patients experienced a DOR that lasted for at least 6 months, and 14% had a response that lasted for at least 12 months. The median time to response was 2.5 months (range, 0.7-7.4).

"Futibatinib is an effective, well-tolerated therapy for patients with intrahepatic cholangiocarcinoma that can be taken orally," Tim Whitten, president and chief executive officer of Taiho Oncology, Inc., stated in a press release.² "This approval is an important milestone for patients and may provide hope for improved outcomes. As someone whose family has been impacted by cholangiocarcinoma, I'm acutely aware of the impact this disease can have on the patient and their loved ones."

Study participants received oral futibatinib at 20 mg once daily until progressive disease or intolerable toxicity.³

The major efficacy measures for the trial included ORR and DOR per ICR and by RECIST v1.1 criteria.

The median age of these patients was 58 years (range, 22-79), with 22% of patients at least 65 years of age. Moreover, 56% of patients were female and 50% were White. Regarding ECOG performance status at baseline, 47% had a status of 0 and 53% had a status of 1. More than half of patients (78%) had in-frame FGFR2 gene fusions; the most common fusion partner was BICC1, which was observed in 23% of patients. Additionally, 22% of patients harbored other FGFR2 arrangements that may not have been in-frame with the partner gene or the partner gene was not identifiable.

Regarding prior treatment, all patients and previously received 1 prior systemic therapy; 30% and 23% of patients received 2 prior lines or 3 or more prior lines, respectively. All participants had previously received platinum-based therapy, with 91% of patients having received gemcitabine plus cisplatin.

Safety was evaluated in 103 patients. The median duration of treatment was 9 months (range, 0.5-25).

Thirty-nine percent of patients experienced serious toxicities, which included pyrexia (3.9%), gastrointestinal hemorrhage (3.9%), ascites (2.9%), musculoskeletal pain (2.9%), and bile duct obstruction (2.9%).

Sixty-six percent of patients experienced dosage interruptions because of an adverse reaction. Adverse reactions that resulted in dosage interruption were hyperphosphatemia, palmar-plantar erythrodysesthesia syndrome, increased alanine aminotransferase, increased aspartate aminotransferase, and fatigue.

Moreover, 58% of patients required dose reduction because of toxicities such as hyperphosphatemia, palmar-plantar erythrodysesthesia syndrome, fatigue, increased alanine aminotransferase, increased aspartate aminotransferase, nail toxicity, and stomatitis.

The most common toxicities reported with futibatinib, that occurred in at least 20% of patients, included nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, abdominal pain, dry skin, arthralgia, dysgeusia, dry eye, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting.

References

1. FDA grants accelerated approval to futibatinib for cholangiocarcinoma. News release. FDA. September 30, 2022. Accessed September 30, 2022. https://bit.ly/3rjADMD
2. FDA approves Taiho's Lytgobi (futibatinib) tables for previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma. News release. Taiho Oncology, Inc. September 30, 2022. Accessed September 30, 2022. https://prn.to/3y2s7W8
3. Lytgobi. Prescribing information. Taiho Oncology, Inc; 2022. Accessed September 30, 2022. https://bit.ly/3BXxase