FDA Grants Accelerated Approval to Infigratinib for Metastatic Cholangiocarcinoma

The FDA granted accelerated approval to the kinase inhibitor infigratinib (Truseltiq) for the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma (CCA) that harbors an FGFR2 fusion or other rearrangement.

The approval was based on efficacy results from a phase 2, multicenter, open-label, single-arm clinical trial in which 108 patients with unresectable locally advanced or metastatic CCA and an FGFR2 fusion or rearrangement were treated with once-daily oral infigratinib 125 mg in 28-day cycles (21 consecutive days of treatment, followed by 7 days with no treatment).

All patients had received ≥1 previous treatments for CCA. For the trial, treatment continued until disease progression or unacceptable toxicity. Nearly all (99%) patients in the trial had stage IV CCA.

The primary study end points were overall response rate (ORR) and the duration of response (DOR), as determined by blinded Independent Central Review according to RECIST version 1.1.

The ORR was 23% (95% confidence interval [CI], 16-32), which included 24 partial responses and 1 complete response.

The median DOR was 5 months (95% CI, 3.7-9.3), with 8 of 23 responders maintaining a response for ≥6 months.

In a news release from QED Therapeutics and Helsinn Group that accompanied the FDA approval of infigratinib, Susan Moran, MD, MSCE, Chief Medical Officer for QED Therapeutics, said, “This is an important milestone for patients diagnosed with FGFR2 fusion–driven cholangiocarcinoma who have recurred after first-line therapy and are in need of targeted options for further treatment. Based on the efficacy seen to date, our team believes infigratinib possesses promise for a range of FGFR-driven conditions, including other cancers.”

During the study, the most common adverse reactions (observed in ≥20% of patients) were hyperphosphatemia, increased creatinine, nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmar-plantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, vision blurred, and vomiting.

Serious risks identified in the study include hyperphosphatemia and retinal pigment epithelial detachment.

CCA News Editor-in-Chief Milind M. Javle, MD, Professor of Gastrointestinal Medical Oncology at The University of Texas M.D. Anderson Cancer Center, presented these study results at the 2021 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

In the news release related to the FDA approval, Dr Javle noted that although “targeted treatments have extended survival for many types of cancer, people diagnosed with cholangiocarcinoma have previously been presented with extremely limited treatment options coupled with low statistical survival data.”

These study results confirmed that “infigratinib showed promise as a targeted treatment option for patients with FGFR2 fusion–driven cholangiocarcinoma with a well-tolerated safety profile in line with previous observations in this patient population,” Dr Javle added.