• Erdafitinib(JNJ-42756493)是一种有效的口服pan-FGFR酪氨酸激酶抑制剂;
  • 11例FGFR畸变胆管癌(CCA)接受治疗(一期临床实验);
  • 常见不良反应:口腔炎(82%),高磷血症(64%),口干(55%),味觉障碍(45%)、皮肤干燥(45%)、乏力(45%),主要为1-2级。
  • 客观反应率为27.3%,另有27.3%病情稳定,疾病总控制率为55%;
  • Erdafitinib治疗晚期CCA和FGFR畸变具临床活性且毒性很小。

Safety and activity of the pan-fibroblast growth factor receptor (FGFR) inhibitor erdafitinib in phase 1 study patients (Pts) with molecularly selected advanced cholangiocarcinoma (CCA)



Abstract & Authors:展开

Background: Erdafitinib (JNJ-42756493) is a potent, oral pan-FGFR tyrosine kinase inhibitor that demonstrated encouraging preliminary clinical activity and manageable adverse events (AEs) in its first-in-human phase 1 study in advanced solid tumors (NCT01703481). Here we report results from pts with CCA from this study.
Methods: This 4-part study enrolled pts age ≥ 18 years (y) with advanced solid tumors. Dose escalation (part 1) followed a 3+3 design, with pts receiving ascending doses of erdafitinib continuously or intermittently (7 days on/7 days off). Subsequent parts required FGFR gene alterations in the tumor, including activating mutations and translocations or other FGFR-activating aberrations. Part 2 was a pharmacodynamics cohort. Parts 3 and 4 were dose-expansion cohorts for recommended phase 2 doses of 9 mg once daily (QD) and 10 mg intermittently, respectively.
Results: Eleven pts with FGFR-aberrant CCA were treated at 9 mg QD (n = 1) or 10 mg intermittent (n = 10). Median age was 60 y; 7 of 11 pts were female (64%). 73% of pts had ECOG performance status 1. All had prior systemic therapy. Median treatment duration with erdafitinib was 5.3 months (mo). Systemic erdafitinib exposure, per Cmax and AUC, in CCA pts was similar to other indications. The most common AEs were stomatitis (82%), hyperphosphatemia (64%), dry mouth (55%), dysgeusia (45%), dry skin (45%), and asthenia (45%), mostly grade 1/2 severity. No drug-related grade ≥3 AEs were reported in > 1 pt except grade 3 stomatitis (n = 2; 18%). The objective response rate, all confirmed partial responses (PRs) per RECIST 1.1, was 27.3% (3/11; 95% CI 6, 61); an additional 27.3% (3/11) had stable disease as their best response. Overall disease control rate was 55%. All 3 PRs were at the 10 mg intermittent dosage, and the median duration of response was 12.9 mo. With a median follow-up of 5.1 mo, median progression-free survival was 5.1 mo (95% CI 1.6, 16.4). As of the cutoff date, 2 pts continue on study treatment.
Conclusions: Erdafitinib showed encouraging clinical activity and minimal toxicity in pts with advanced CCA and FGFR alterations. These results warrant further study.

All Authors:
Jean-Charles Soria