Dose and schedule for checkpoint inhibitors and agonists

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Should ph1/2 development actively interrogate low dose/infrequent dosing of IO agonists?
How should patient visits be optimized if drugs are on different schedules?
Competititve advantages, potential anti-competitive issues for FDA to consider for single vial formulation for two biologics?
Impact of bispecifics for combination therapies?

Raphael Clynes
78 months ago

2 answers

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Yes, this is important to investigate such questions in early phases to allocate future dose et effects.

Franck PAVAN
78 months ago
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I agrre perfectly with Dr Pavan. Establishing the optimal dosing regimen of checkpoint inhibitors is very important.
For example, Combination anti-CTLA-4 and anti-PD-1 therapy is currently dosed as same-day ipilimumab (3 mg/kg) followed by nivolumab (1 mg/kg) every 3 weeks for four doses, followed by nivolumab (240 mg) every 2 weeks thereafter. As this combination regimen is associated with greater toxicity than ICPI monotherapy, alternative dosing strategies are being evaluated in clinical studies with the objective of improving the safety/efficacy profile, including lower-dose anti-CTLA-4 antibodies in combination with anti-PD-1/anti-PD-L1 antibodies (nivolumab + ipilimumab,54 pembrolizumab + ipilimumab,55 durvalumab + tremelimumab). Unlike chemotherapy where it is typical to dose-reduce patients to manage toxicities, the only dose modifications currently allowed with ICPIs are to either delay or discontinue therapy.

Pietro Carotenuto
78 months ago

Have some input?