Early data show promise for the FGFR inhibitor rogaratinib
medwireNews: The fibroblast growth factor receptor (FGFR) inhibitor rogaratinib is well tolerated and clinically active in patients with various tumor types selected for treatment on the basis of FGFR mRNA overexpression, phase I study data show.
Martin Schuler (University of Duisburg-Essen, Germany) and colleagues explain that genetic alterations have previously been used as predictive biomarkers in the clinical development of FGFR inhibitors, but their prevalence is typically low.
The current study therefore suggests that “FGFR mRNA positivity could be a clinically useful biomarker in addition to genetic alterations, identifying more patients who are likely to be susceptible to FGFR inhibition,” they write in The Lancet Oncology.
Overall, 866 patients with advanced solid cancers were screened for FGFR mRNA overexpression during the study, with rates ranging from 2% for colorectal cancer to 47%, 50%, and 57% for squamous non-small-cell lung cancer (NSCLC), urothelial carcinoma, and head and neck squamous cell carcinoma (HNSCC), respectively.
Of the patients screened, 23 unselected for FGFR mRNA were included in the dose-escalation phase of the study and received rogaratinib orally twice daily at doses of 50–800 mg in continuous 21-day cycles.
During this phase there were no dose-limiting toxicities and the maximum tolerated dose was not reached. Therefore, 800 mg twice daily was established as the recommended phase II dose and was used in the dose-expansion phase of the study, which included 103 patients with FGFR mRNA-overexpressing tumors (52 urothelial carcinoma, 20 NSCLC, eight HNSCC, and 23 other solid tumor types).
During a median 12 weeks of treatment overall, all 126 patients experienced at least one treatmentemergent adverse event of any grade, most commonly hyperphosphatemia (61%), diarrhea (52%), and decreased appetite (38%). The most common grade 3–4 adverse events, seen in 29% of patients, were fatigue (10%) and asymptomatic increased lipase (8%).
In the expansion cohorts, 15% of 100 evaluable patients achieved an objective response, and 71% achieved disease control.
The highest objective response rate was seen among the patients with urothelial carcinoma, at 24%, including six responses among patients with no FGFR genetic alterations and three responses among patients with no substantial clinical benefit from previous immune checkpoint inhibitors.
A further 49% of patients with urothelial carcinoma had stable disease, giving a disease control rate of 73%.
In addition, four of 14 patients with urothelial carcinoma who had progressive disease were subsequently found to be PIK3CA or RAS mutation carriers. Excluding these patients increased the objective response rate from 24% to 27%, the researchers note.
Among the other disease cohorts, one patient in each had a partial response and 31 had stable disease (15 NSCLC, two HNSCC cohort, and 14 other solid tumors).
Schuler et al conclude that “rogaratinib treatment in patients selected by overexpression of FGFR1–3 mRNA is a promising new option in precision oncology for the treatment of advanced cancers.”
By Laura Cowen
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