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.
Presented by: Yohann Loriot, MD, PhD
Co Authors: 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, On Behalf of the BLC2001 Study Group; Institut Gustave Roussy, Villejuif, France; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South); Clara Campal Comprehensive Cancer Center, Madrid, Spain; Institute of Cancer Research, Sutton, United Kingdom; Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC; Virginia Oncology Associates, US Oncology Research, Norfolk, VA; Norton Healthcare, Louisville, KY; Hospital Clinic de Barcelona, Barcelona, Spain; Altai Regional Cancer Center, Barnaul, Russia; Penn State Health Milton S. Hershey Medical Center, Hershey, PA; Hospital Universitario Virgen del Rocio, Seville, Spain; Janssen Research & Development, LLC, Spring House, PA; Janssen Research & Development, LLC, Beerse, Belgium; UT MD Anderson Cancer Center, Houston, TX
Presented at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA