medwireNews: Adding the novel anti-PD-1 agent cetrelimab to the pan-FGFR inhibitor erdafitinib doubles the response rate in cisplatin-ineligible patients with untreated locally advanced or metastatic urothelial cancer and FGFR alterations, indicate trial data.
Speaking at the ESMO Congress 2021, investigator Thomas Powles (Barts Cancer Institute, London, UK) highlighted the “significant unmet need” regarding treatment options for people with advanced urothelial cancer who are ineligible for cisplatin.
He explained that there is “a strong rationale” for combining erdafitinib and cetrelimab, as “[n]eoantigen release by erdafitinib may prime the tumor microenvironment for response” to immune checkpoint blockade, ultimately resulting in synergy.
Thomas Powles explains why the interim results of the NORSE trial justify the continuance of first-line cetrelimab plus erdafitinib in FGFR-altered advanced urothelial cancer (2:23)
Powles reported on an interim analysis of the phase 2 part of the NORSE trial that included 53 patients with newly diagnosed locally advanced or metastatic urothelial cancer positive for FGFR mutations or fusions. Participants were randomly assigned to receive intravenous cetrelimab at a dose of 240 mg every 2 weeks for four cycles and at 480 mg every 4 weeks subsequently alongside erdafitinib 8 mg/day or erdafitinib alone at the same dose, albeit with pharmacodynamically-guided uptitration to 9 mg.
The primary endpoint of overall response was achieved by 68% of the 19 evaluable patients in the cetrelimab plus erdafitinib group and 33% of the 18 evaluable patients in the erdafitinib alone group. The complete response rates were 21% and 6%, respectively.
The median duration of response was 6.9 months among patients who received cetrelimab plus erdafitinib and was unreached among those given erdafitinib alone. Responses were ongoing at the time of analysis in 10 of the 13 responders in the combination arm and five of the six responders in the monotherapy arm.
The safety profile of the combination “was generally similar to that of erdafitinib alone,” said Powles, with grade 3–4 treatment-emergent adverse events (TEAEs) occurring in 50% of combination-treated patients and 38% of those given erdafitinib alone. The most common events of this severity in the combination arm were stomatitis and lipase elevations, each in 12.5% of patients, while anemia and general physical deterioration were most common in the monotherapy arm, also at 12.5% each.
Drug-related TEAEs led to discontinuation of cetrelimab, erdafitinib, or both in 29% of the group, whereas the discontinuation rate in the erdafitinib group was 8%. One death in the combination arm, a case of respiratory failure, was deemed to be related to cetrelimab.
“These data suggest potential positive interaction between erdafitinib and cetrelimab” in this patient population, and “[e]nrollment in NORSE is ongoing and supported by these data,” concluded the presenter.
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This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany