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Background Exposure–response analyses were conducted to explore the relationship between selected efficacy and safety endpoints and serum phosphate (PO4) concentrations, a potential biomarker of efficacy and safety, in locally advanced or metastatic urothelial carcinoma patients with FGFR alterations treated with erdafitinib. Methods Data from two dosing regimens of erdafitinib in a phase 2 study (NCT02365597), 6 and 8-mg/day with provision for pharmacodynamically guided titration per serum PO4 levels, were analyzed using Cox proportional hazard or logistic regression models. Efficacy endpoints were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Safety endpoints were adverse events typical for FGFR inhibitors. Results Exposure-efficacy analyses on 156 patients (6-mg = 68; 8-mg = 88) showed that patients with higher serum PO4 levels within the first 6 weeks showed better OS (hazard ratio 0.57 [95% CI 0.46–0.72] per mg/dL of PO4; p = 0.01), PFS (hazard ratio 0.80 [0.67–0.94] per mg/dL of PO4; p = 0.01), and ORR (odds ratio 1.38 [1.02–1.86] per mg/dL of PO4; p = 0.04). Exposure-safety analyses on 177 patients (6-mg = 78; 8-mg = 99) showed that the incidence of selected adverse events associated with on-target off-tumor effects significantly rose with higher PO4. Conclusions The exploratory relationship between serum PO4 levels and efficacy/safety outcomes supported the use of pharmacodynamically guided dose titration to optimize erdafitinib’s therapeutic benefit/risk ratio. Clinical trial registration number NCT02365597.

The duration of the presence of maternal mumps antibodies in a prospective cohort study is presented. Immunoglobulin G against mumps was portioned with a commercial ELISA test (EuroimmunA (R) anti-mumps Virus AT ELISA, Germany) on samples from 213 mother-child pairs at seven time points between pregnancy and 12 months of age. Non-linear mixed models were used to model maternal antibody decay in infants. The model-based median time to loss of antibodies was 3.6 months. The median child-specific time to loss of antibodies in children of naturally immune women (3.8 months) and children of vaccinated women (2.4 months) differed significantly (p = 0.025). The log antibody level of the mother and the log birth weight were correlated with the duration of maternal antibodies in infants (p < 0.0001). Conclusion: Children of vaccinated women loose maternal mumps antibodies significantly earlier in life compared to children of naturally infected women. If early administration (< 12 months) of the combined measles, mumps, and rubella vaccine is needed, maternal mumps antibodies are not expected to interfere with infant humoral vaccine responses.