At ASCO GU 2018, Dr. Loriot presented the results of erdafitinib, a pan-FGFR inhibitor for patients with mUC and found a confirmed objective response rate of 35% in those receiving erdafitinib continuously.3 Dr. Joerger also presented results of another oral pan-FGFR kinase inhibitor at ASCO GU 2018, rogaratinib. In his biomarker preselected cohort of patients with high FGFR1-3 mRNA expression, objective response rate was 30% (3/10). This abstract provides data on a selective FGFR3 inhibitor, Vofatamab (B-701), for patients with metastatic UC.
Figure 1: Incidence of FGFR3 alterations based on 9 urothelial carcinoma databases.
Generated by Jason Zhu from http://www.cbioportal.org.
This is a phase I/II clinical trial which treated patients with Vofatamab (V) or Vofatamab in combination with docetaxel (VD). Vofatamab is thought to prevent FGFR3 activation via prevention of ligand activation of the FGFR3 receptor as well as preventing mutant/fusion signaling. Patients were required to have a pathogenic FGFR3 mutation or fusion identified using the FoundationONE assay on archival samples. Patients must have had progressed on one or more prior lines of chemotherapy or had progression less than 12 months from neoadjuvant chemotherapy. Vofatamab was dosed at 25 mg/kg and docetaxel was given at 75 mg/m2.
21 patients have received V and 21 patients have received VD. In terms of patient characteristics, the median age was 64 in the combination arm and 70 in the monotherapy arm. 52% of patients had visceral metastases in the VD arm and 43% in the D arm. These patients were heavily pre-treated, with most patients having had 2-3 prior lines of chemotherapy and about half of patients had prior immune checkpoint therapy.
In terms of efficacy, 5 out of 21 patients have had a partial response thus far in the VD arm compared with 1 out of 21 patients in the V arm. The median time to response was 3.5 months in VD and 4 months in V. In terms of safety, the most common treatment-emergent adverse events were decreased appetite, diarrhea, and pyrexia. The most common grade 3 or higher TRAEs was anemia, dyspnea, and fatigue.
In a heavily pre-treated population with metastatic UC, Vofatamab in combination with docetaxel is well tolerated and effective in a small population of patients. Combination therapy appears to have more objective responses than Vofatamab monotherapy. Follow up is immature at this time, but the results presented show that Vofatamab is an active therapy and additional combination are being explored.
Presented by: Andrea Necchi, MD, Medical Director, Istituto Nazionale dei Tumori, Milan, Italy
Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA
References:
- Cappellen D, De Oliveira C, Ricol D, et al. Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nature genetics 1999;23:18.
- van Rhijn BW, Lurkin I, Radvanyi F, Kirkels WJ, van der Kwast TH, Zwarthoff EC. The fibroblast growth factor receptor 3 (FGFR3) mutation is a strong indicator of superficial bladder cancer with low recurrence rate. Cancer research 2001;61:1265-8.
- Loriot Y, Necchi A, Park SH, et al. Erdafitinib (ERDA; JNJ-42756493), a pan-fibroblast growth factor receptor (FGFR) inhibitor, in patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) and FGFR alterations (FGFRa): Phase 2 continuous versus intermittent dosing. American Society of Clinical Oncology; 2018.