English to Russian Law/Patents Medical: Pharmaceuticals Препараты для лечения рака легких

In the dose-escalation phase of the study, MEDI4736 and tremelimumab will be administered initially in sequential cohorts of 3-6 subjects who are immunotherapy-naïve with each subject receiving tremelimumab Q4W for 6 doses and every 12 weeks (Q12W) for 3 doses (i.e., tremelimumab Dose 7 given at 4 weeks from Dose 6 and Dose 8 given at 12 weeks from Dose 7) and MEDI4736 Q4W for 13 doses via IV infusion for a total of one year (Figure 2). Each cohort will enroll a minimum of 3 subjects, according to a standard 3+3 design and a modified zone-based design. Subjects in the first cohort (Cohort 1) will receive a dose of 3 mg/kg MED4736 and 1 mg/kg of tremelimumab. If ≥ 2 dose limiting toxicities (DLTs) are observed in the first dose cohort, the starting dose will be de-escalated per Figure 1. If no more than 1 out of 6 subjects experiences a DLT in a given dose cohort, dose-escalation will continue.


Что-то подобное нашел в этой публикации - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913186/

(iii) a zone-based design, in which we replaced our start-up rule (i.e., dose escalation along diagonal) with the zone-based start-up rule (Huang et al., 2007; Wages et al., 2011). The goal of this comparison is to evaluate the performance of the proposed start-up rule. As shown in Fig. 2, the basic idea of the zone-based start-up rule is that, based on the partial order of the dose-toxicity relationship for the drug combinations, we can divide the dose combination matrix into zones and conduct dose escalation among zones (i.e., if the doses in one zone are deemed safe, we escalate to the next higher zone). For doses within zones, as their toxicity probabilities are not ordered, patients are equally allocated to these doses. The details of the zone-based start-up rule can be found in Huang et al. (2007) and Wages et al. (2011).


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