(UroToday.com) Rogaratinib is an orally available small-molecule inhibitor of FGFR1–4. In the phase 1 study of rogaratinib in patients with advanced solid tumors, the objective response in FGFR mRNA overexpressing tumors was 67% (10/15)1. This study evaluates the combination of rogaratinib with atezolizumab in patients with advanced urothelial carcinoma.
Thirty-one patients were enrolled in the study. Patients had to be cisplatin and eligible with metastatic urothelial carcinoma. Patients were also biomarker selected for high FGFR1 or FGFR3 mRNA, defined as an RANscope score of 3+ or 4+. PIK3CA and RAS encoding genes were assessed with the Illumina MiSeq platform and PD-L1 expression was measured with the 22C3 IHC, with a cutoff defined as TPS>1%. The treatment included Rogaratinib 800 mg orally daily and atezolizumab 1200 mg every 21 days. The primary objective was safety and tolerability as well as determining the safe dose for phase II.
Baseline characteristics are shown above. Most of the patients were male with a median age of 74 and almost all patients had either negative or low PD-L1 expression.
The objective response rate was 44% and 4 (16%) patients had a complete response, with an overall disease control rate of 68%. 6 patients had stable disease. Most patients did not have an FGFR3 mutation. 
In terms of safety, the most common grade 3/4 adverse events included elevated lipase, rash. Treatment-emergent adverse events specific to rogaratinib was hyperphosphatemia (45%) and retinal pigment epithelium detachment (3%). Based on these adverse events, the maximum tolerated dose of rogaratinib was set at 600 mg BID.
The objective response rate to rogaratinib in patients with UC and high FGFR1 or FGFR3 mRNA expression in the study was 44%. This is lower than the prior phase 1 study (67%) but that was a pan-tumor cohort and this is specific to bladder. Four patients had a complete response which is very encouraging. Early biomarker work exploring resistance gene mutations (PIK3CA, HRAS, KRAS, NRAS) showed that no patients with resistance genes had a response (0/3). If you exclude those patients, the ORR was 11/20 (55%). Most patients did not harbor an FGFR3. Additional patients are being enrolled at the maximum tolerated dosage of 600 mg BID.
Presented By: Jonathan E. Rosenberg, MD, Chief of the Genitourinary Medical Oncology Service, Division of Solid Tumor Oncology; and the Enno W. Ercklentz Chair at Memorial Sloan Kettering Cancer Center, New York City, NY
Written by: Jason Zhu, MD. Medical Oncologist, Division of Genitourinary Cancers, Levine Cancer Institute, Twitter: @TheRealJasonZhu, at the 2020 ASCO Annual Meeting, Virtual Scientific Program #ASCO20, May 29-31, 2020.
References:
- Schuler M, Cho BC, Sayehli CM, et al. Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and dose-expansion study. The Lancet Oncology 2019;20:1454-66.