Exposure-response relationship of nivolumab and ipilimumab in patients with metastatic renal cell carcinoma from the randomised phase 2 BIONIKK study
Mené sur 110 patients atteints d'un carcinome rénal de stade métastatique, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du nivolumab avec ou sans ipilimumab
Background: We aimed to investigate the exposure-response (E/R) relationship for ipilimumab and nivolumab in metastatic clear cell renal cell carcinoma (m-ccRCC) patients from the randomised phase 2 BIONIKK trial (EudraCT 2016-003099-28).
Methods: This study included patients treated with either single-agent nivolumab (Nivo monotherapy group, n = 39) or nivolumab plus ipilimumab (Ipi/Nivo group, n = 71). Trough plasma concentrations (Cmin) were assayed at week 6 after treatment start. Cox proportional hazard and logistic regression models were used to investigate the E/R relationship between Cmin and clinical outcomes.
Results: Low nivolumab Cmin (<median) was not identified as an independent risk factor for progression in either the Nivo monotherapy group (HR 2.03, 95% CI [0.93–4.44]; p = 0.076) or the Ipi/Nivo group (HR 1.06, 95% CI [0.63–1.79]; p = 0.83). Interestingly, low ipilimumab Cmin (<4.9 µg/mL) was independently associated with worse PFS in the Ipi/Nivo group (HR 1.77, 95% CI [1.03–3.05]; p = 0.040). In both groups, neither nivolumab Cmin nor ipilimumab Cmin was associated with the risk of death or grade ≥ 3 TRAEs occurrence.
Conclusions: This study suggests an E-R relationship for the efficacy of ipilimumab in m-ccRCC patients treated in combination with nivolumab. Prospective validation of our efficacy threshold in larger cohorts or phase 3 trials is essential prior to the implementation of a pharmacokinetically guided strategy.
British Journal of Cancer , résumé, 2026