Updated results of a phase IIa study to evaluate the clinical efficacy and safety of erdafitinib in Asian advanced cholangiocarcinoma (CCA) patients with FGFR alterations.

Abstract

4117 Background: Patients (pts) with advanced CCA who progressed on or after first line chemotherapy have no approved treatment options. Fibroblast growth factor receptor (FGFR) gene alterations are observed in many tumor types including 14-17% in CCA. Erdafitinib, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown clinical activity against solid tumors with FGFR alterations. Methods: LUC2001 is an open-label, multicenter, Ph2a study in advanced CCA pts with FGFR alterations (FoundationOne), who progressed after ≥ 1 prior treatment. The primary endpoint is objective response rate (ORR; RECIST 1.1). The secondary endpoints are disease control rate (DCR), progression free survival (PFS), duration of response (DOR), safety and pharmacokinetics (PK). Disease is evaluated every 8 weeks until disease progression (PD). Results: As of 3 Dec 2018, 222 CCA pts were molecularly screened; 34 had FGFR alterations, of whom 14 (8 FGFR2 fusion, 3 FGFR2 mutation, 1 FGFR3 fusion, 2 FGFR3 mutation) were dosed 8 mg once daily with up titration option. Median age was 51.5 years. 13/14 and 12/14 pts had prior platinum or gemcitabine based therapy respectively, 7/14 pts got re-treated with platinum or gemcitabine based therapy, and 9/14 pts had ≥2 prior lines of therapy. Median number of treatment cycles was 5.0 (range: 1; 22) and treatment duration was 4.83 (range: 0.5; 20.3) months. In 12 evaluable pts, there were 6 confirmed partial response (PR), 4 stable disease (SD) and 2 PD; ORR (CR+PR) was 6/12 (50.0%), DCR (CR+PR+uCR+uPR+SD) was 10/12 (83.3%); median DOR was 6.83 months (95% CI: 3.65; 12.16); median PFS was 5.59 months (95% CI: 1.87, 13.67). In 10 evaluable FGFR2+ pts, ORR was 6/10 (60.0%); DCR was 10/10(100%); median PFS was 12.35 months (95% CI: 3.15, 19.38). The most common TEAEs ( > 30%) were hyperphosphatemia, dry mouth, stomatitis, and dry skin. 9 pts had ≥ Grade 3 AEs (8 Grade 3,1 Grade 5), of which 7 drug related. TEAE led to treatment 1 discontinuation, 6 dose reductions and 1 death (not drug related). The results of PK and PK/PD relationship were consistent with other erdafitinib studies in different ethnic background pts. Conclusions: Asian advanced CCA pts with FGFR alterations treated with erdafitinib had encouraging efficacy and acceptable safety profile similar to experience in other tumor types and populations. Clinical trial information: NCT02699606.

Therapy of Primary Liver Cancer

“…139 Asian advanced cholangiocarcinoma patients with FGFR alterations treated with erdafitinib in a phase IIa study (NCT02699606) showed promising efficacy and manageable safety profiles similar to those with other tumor types. 140 Debio 1347. Debio 1347 is a novel orally administered small molecule that is a highly selective FGFR1-3 ATP-competitive inhibitor.…”

FGFR inhibitors in cholangiocarcinoma: what’s now and what’s next?

“… 36 In CCA, a phase I as well as a phase IIa study in Asian patients showed promising results for erdafitinib, but due to the low patient numbers the clinical data available thus far cannot be considered fully conclusive yet [ClinicalTrials.gov identifier: NCT01703481] and [ClinicalTrials.gov identifier: NCT02699606]. 37 – 39 Clinical trial data on FGFR inhibitors in iCCA are summarized in Table 1 .…”

Broadening the therapeutic horizon of advanced biliary tract cancer through molecular characterisation

“…These promising results have prompted a randomised phase III study of infigratinib against gemcitabine and cisplatin in patients with advanced CCA with FGFR2 fusions (PROOF trial, NCT03773302). Similarly, erdafitinib (JNJ-42756493), another potent oral pan-FGFR inhibitor, has also indicated efficacy with an ORR of 50% when assessed in an Asian cohort of 12 evaluable patients with advanced FGFR-altered CCA [64]. The FIGHT-202 study provided further proof-of-concept to support the use of FGFR inhibitors in FGFR2-fusion-positive patients, as results from this phase II study have shown that radiological responses were limited to patients harbouring FGFR2 fusions or rearrangements (ORR 35.5%, n = 38), with no responses seen in patients with other FGFR2 alterations or wildtype patients [65].…”

“…These results have provided the rationale for a randomised phase III trial of pemigatinib against standard first-line chemotherapy in patients with FGFR2-translocated advanced CCA (NCT03656536). The toxicity profiles of infigratinib, pemigatinib and erdafitinib demonstrate a degree of overlap and include hyperphosphataemia, fatigue and stomatitis as frequently occurring side-effects [64][65][66]. Hyperphosphataemia is an on-target effect related to FGF23regulated phosphate homeostasis and has been found to be manageable with diet modification and phosphate-binding therapies [65].…”