Institut Gustave Roussy, Villejuif, France
Yohann Loriot , Andrea Necchi , Se Hoon Park , Jesús García-Donas , Robert A Huddart , Earle Frederick Burgess , Mark T. Fleming , Arash Rezazadeh , Begona Mellado , Sergei Varlamov , Monika Joshi , Ignacio Duran , Anne OHagan , Anjali Narayan Avadhani , Bob Zhong , Kim Stuyckens , Anne-Gaëlle Dosne , Arlene O. Siefker-Radtke
Background: Although immune checkpoint inhibitors (ICI) have improved outcomes in some pts with platinum-resistant mUC, many pts (eg, pts with TCGA luminal 1 tumors, many of whom are FGFRa) may not benefit. ERDA, a pan-FGFR (1-4) inhibitor, demonstrated promising phase 1 activity: 11 partial responses among 24 FGFRa mUC pts. We report efficacy and safety of ERDA in the ongoing global open-label phase 2 study BLC2001 (NCT02365597). Methods: Pts had measurable mUC with specific FGFR2/FGFR3 mutations or translocations per central lab Janssen assay, ECOG 0-2, and were chemorefractory (progressed during/following ≥ 1 line of prior systemic chemo or ≤ 12 mos of [neo]adjuvant chemo). Cisplatin-ineligible, chemo-naïve pts, and prior ICI treatment were allowed. Pts were randomized 1:1 to 28-d cycles of oral 6 mg/d continuous dosing (6 C) or 10 mg/d intermittent 7 d on/7 d off dosing (10 I) ERDA; the dose was further uptitrated if no significant treatment-related adverse events (TRAEs) were observed. The primary end point was ORR. Results: 78 pts received 6 C and 33 pts received 10 I (10 I cohort stopped early) ERDA. 31 pts in 6 C arm were further uptitrated. Across arms, 50% had ≥ 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 (Table). Treatment is ongoing in 10 pts. Conclusions: ERDA (6 C or 10 I) has promising efficacy and tolerability in pts with FGFRa mUC. Based on these results and ERDA pharmacometric modeling, dosing was optimized at 8 mg/d (continuous), and this cohort is ongoing. Phase 3 study is planned. Clinical trial information: NCT02365597
AEs, n (%) | ERDA | |||||
---|---|---|---|---|---|---|
6 C | 10 I | |||||
Serious TRAEs | 3 (4) | 0 | ||||
Discontinuations due to TRAEs | 9 (12) | 4 (12) | ||||
Gr 1-2 | Gr 3 | Gr 4-5 | Gr 1-2 | Gr 3 | Gr 4-5 | |
Most common TRAEs, any grade (gr) | ||||||
Hyperphosphatemia | 46 (59) | 0 | 0 | 14 (42) | 0 | 0 |
Diarrhea | 34 (44) | 0 | 0 | 12 (36) | 1 (3) | 0 |
FGFR inhibitor class effect AEs (summed terms) | ||||||
Nail AEs | 24 (31) | 4 (5) | 0 | 9 (27) | 1 (3) | 0 |
Skin AEs | 37 (47) | 0 | 0 | 13 (39) | 0 | 0 |
Eye AEs | 30 (38) | 3 (4) | 0 | 15 (45) | 0 | 0 |
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