FDA Approves FoundationOne CDx as Pemigatinib Companion Diagnostic in FGFR2+ Cholangiocarcinoma

The FDA has approved FoundationOne CDx as the registrational companion diagnostic for pemigatinib (Pemazyre), which the agency recently approved for the treatment of adult patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement as detected by an FDA-approved test.¹

The test is the only approved companion diagnostic for this indication. Overall, FoundationOne CDx is approved as a companion diagnostic across numerous cancer types for a total of 20 different treatments.

“The approval of this therapy and companion diagnostic is an important step forward in advancing care for patients with cholangiocarcinoma for whom there are limited treatment options,” Brian Alexander, MD, MPH, chief medical officer at Foundation Medicine, said in a press release. “The breadth and depth of our sequencing allows for identification of patients with this rare fusion who may benefit from Pemazyre, underscoring the importance of comprehensive genomic profiling in cholangiocarcinoma. We continue to work toward broadening patient access to biomarker-driven therapies, illustrated by this recent milestone. We are proud to add another important FDA-approved companion diagnostic to FoundationOne CDx.”

On April 17, the FDA approved pemigatinib for the treatment of patients with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements, as detected by an FDA-approved test.

The approval was based on interim findings from the multicohort, single-arm, phase II FIGHT-202 study, which showed that, at a median follow-up of 15 months, single-agent pemigatinib led to a 36% objective response rate (ORR) and a median duration of response of 7.5 months in a cohort of patients with FGFR2 fusions or rearrangements. ^2,3 The selective inhibitor of FGFR1, 2, and 3 was also associated with a manageable adverse event (AE) profile.

The FIGHT-202 trial was conducted in the United States, Europe, Middle East, and Asia. Patients who were eligible for enrollment had locally advanced or metastatic cholangiocarcinoma despite ≥1 line of prior therapy, had their FGF/FGFR status centrally confirmed, and adequate renal function was required.

Patients were stratified into 3 cohorts: those with FGFR2 fusions/rearrangements (cohort A; n = 107), those with other FGF/FGFR genetic alterations (cohort B; n = 20), and no FGF/FGFR alterations (cohort C; n = 18). Patients in each of the 3 cohorts were treated with oral pemigatinib (13.5 mg) using a 2-weeks-on/1-week-off schedule.

The study was not designed to make statistical comparisons between the 3 cohorts. The primary endpoint was the confirmed ORR in cohort A by independent central review.

Median age of the entire 146 patients who were enrolled was 59 years; however, 77% of patients in cohort A were <65 years, compared with 50% in cohort B, and 39% of patients in cohort C. Overall, 58% of patients were women (61% in cohort A), and 61% of patients were enrolled in North America, 24% in Western Europe, and 15% of patients were enrolled in other geographical areas.

Among the 107 patients in cohort A, 92 fusions and 15 rearrangements identified. A total of 56 unique fusion partners were identified, the most common of which was BICC1, which occurred in 29%. Forty-two partners were unique to a single patient, and no fusion partner was identified in 5% of patients.

Results showed that, in cohort A, the 36% ORR consisted of 3 (2.8%) complete responses, 35 (33%) partial responses, and 50 (46.7%) patients with stable disease, for a disease control rate of 82%. The ORR was consistent across subgroups, including when stratified by the number of prior lines of therapy and by FGFR2 rearrangement partner. Among those who had a response, 24 patients (63%) had a response lasting ≥6 months and 7 patients (18%) had a response lasting ≥12 months.

Additionally, the higher ORR translated into a longer median progression-free survival (PFS) in cohort A. Median PFS was 6.9 months in cohort A compared with 2.1 months in cohort B and 1.7 months in cohort C.

Overall survival (OS) data were not yet mature at the time of the March 22, 2019, data cutoff. However, but with a median duration of follow-up of 15.4 months and a median duration of treatment of 7.2 months, the median OS was 21.1 months in the cohort with FGFR2 fusions/rearrangements. Median OS was only 6.7 months in the cohort with other FGF/FGFR alterations after a median follow-up of 19.9 months, and only 4.0 months in the cohort without an FGF/FGFR alteration after a median follow-up of 24.2 months.

Regarding safety, AEs were found to be manageable and consistent with the mechanism of action of pemigatinib. The most common AE was hyperphosphatemia (60%), but no grade ≥3 cases were encountered. Hyperphosphatemia was managed with a low phosphate diet, phosphate binders, diuretics, and a reduction or interruption in the pemigatinib dose. Three patients required dose reductions/interruptions due to hyperphosphatemia.

References

1. Foundation Medicine Receives FDA Approval for FoundationOne®CDx as the Companion Diagnostic for Pemazyre™ (pemigatinib), the First FDA-Approved Targeted Therapy for Adults with Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma. Posted April 20, 2020. https://bit.ly/3aqhNZx. Accessed April 20, 2020.
2. Hollebecque A, Borad M, Sahai V, et al. FIGHT-202: a phase 2 study of pemigatinib in patients (pts) with previously treated locally advanced or metastatic cholangiocarcinoma (CCA). Presented at: 2019 ESMO Congress; September 27-October 1, 2019; Barcelona, Spain. Abstract LBA40.
3. Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study [published online March 20, 2020]. Lancet Oncol. doi: 10.1016/S1470-2045(20)30109-1