A randomized, controlled trial evaluating the efficacy and safety of BTH1677 in combination with bevacizumab, carboplatin, and paclitaxel in first-line treatment of advanced non-small cell lung cancer

Table 6 Summary of BTH1677 pharmacokinetics parameters

Parameters	Geometric Mean (CV%)
	BTH1677/Bevacizumab/ Carboplatin/Paclitaxel
	Cycle 1/Day 1	Cycle 3/Day 1
N	53^b	42
AUC_0–last (μg•hr./mL)	614.6 (52.0)	423.5 (48.1)
AUC_0–24 (μg•hr./mL)	399.8 (37.3)	464.4 (38.9)^d
AUC_0–∞ (μg•hr./mL)	635.9 (49.5)^c	518.6 (42.2)^e
C_max (μg/mL)	49.77 (36.1)	60.50 (49.2)
CL (L/h)	0.441 (47.3)^c	0.548 (41.6)^e
t_1/2 (hr)	17.56 (36.9)^c	7.17 (35.3)^e
t_max (hr)^a	2.48 (1.52, 5.90)	2.37 (1.92, 6.88)
V_ss (L)	5.37 (42.4)^c	4.13 (51.5)^e
R (AUC)	NA	1.10 (27.3)^d

Abbreviations: AUC_(0-last) area under the serum concentration-time curve from time 0 to the time of the last measurable concentration, AUC_0–24 area under the serum concentration-time curve from time 0 to 24 h, AUC_0–∞ area under the serum concentration-time curve from time 0 to infinity, C_max maximum serum concentration, CL systemic clearance, CV coefficient of variation, hr. hour, L liter, mL milliliter, N overall sample size, NA not applicable, R (AUC) accumulation ratio calculated as AUC_0-24 (Cycle 3)/AUC_0-24 (Cycle 1), t_1/2 elimination half-life, t_max time of maximum concentration, μg microgram, V_ss volume of distribution at steady-state
^aMedian (range)
^bAlthough 2 other patients met the basic criteria for inclusion in the PK population (ie, having at least 75% of the PK measurements available for any particular treatment cycle data set), 2 patients were subsequently excluded from analysis. One patient received a second unplanned BTH1677 infusion on Day 2 of Cycle 1 and a second patient had a longer infusion time (5.58 h) relative to the other patients for Cycle 1/Day 1. Both of these differences were deemed to likely result in PK differences relative to other patients in Cycle 1 and were excluded
^cN = 50
^dN = 37
^eN = 31