Urology Xagena

Erdafitinib, a pan-FGFR inhibitor, in patients with metastatic or unresectable urothelial carcinoma and FGFR alterations

Although immune checkpoint inhibitors ( ICI ) have improved outcomes in some patients with Platinum-resistant metastatic urothelial carcinoma ( mUC ), many patients ( eg, patients with TCGA luminal 1 tumors, many of whom are FGFRa [ FGFR alterations ] ) may not benefit.

Erdafitinib, a pan-FGFR ( fibroblast growth factor receptor ) inhibitor, demonstrated promising phase 1 activity: 11 partial responses among 24 FGFRa mUC patients .

Researchers have reported efficacy and safety of Erdafitinib in the ongoing global open-label phase 2 study BLC2001.

Patients had measurable metastatic urothelial carcinoma with specific FGFR2/FGFR3 mutations or translocations per central lab Janssen assay, ECOG 0-2, and were chemorefractory ( progressed during/following greater than or equal to 1 line of prior systemic chemo or less than or equal to 12 months of [neo]adjuvant chemotherapy ).

Cisplatin-ineligible, chemotherapy-naïve patients, and prior immune checkpoint inhibitors treatment were allowed.
Patients were randomized 1:1 to 28-day cycles of oral 6 mg/d continuous dosing ( 6 C ) or 10 mg/day intermittent 7 day on/7 day off dosing ( 10 I ) Erdafitinib; the dose was further uptitrated if no significant treatment-related adverse events ( TRAEs ) were observed.

The primary end point was overall response rate ( ORR ).

78 patients received 6 C and 33 patients received 10 I ( 10 I cohort stopped early ) Erdafitinib.
31 patients in 6 C arm were further uptitrated.

Across arms, 50% had greater than or equal to 2 prior lines of therapy; 93% were chemorefractory.

Confirmed ORRs ( RECIST 1.1 ) were 35% and 24%, and disease control rates ( CR+PR+SD ) were 74% and 73% in the 6 C and 10 I arms, respectively.

Adverse events ( AEs ) were manageable, and there were no treatment-related deaths.

Treatment is ongoing in 10 patients.

In conclusion, Erdafitinib ( 6 C or 10 I ) has promising efficacy and tolerability in patients with FGFRa metastatic urothelial carcinoma.
Based on these results and Erdafitinib pharmacometric modeling, dosing was optimized at 8 mg/day ( continuous ), and this cohort is ongoing.( Xagena )

Source: BLC2001 Study Group - Genitourinary Cancers Symposium, 2018