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Table 3 Summary of GFH018 PK parameters

From: First-in-human study of GFH018, a small molecule inhibitor of transforming growth factor-β receptor I inhibitor, in patients with advanced solid tumors

 

GFH018

5 mg BID

14d-on/14d-off

GFH018

10 mg BID

14d-on/14d-off

GFH018

20 mg BID

14d-on/14d-off

GFH018

30 mg BID

14d-on/14d-off

GFH018

40 mg BID

14d-on/14d-off

GFH018

50 mg BID

14d-on/14d-off

GFH018

65 mg BID

14d-on/14d-off

GFH018

85 mg BID

7d-on/7d-off

GFH018

85 mg BID

14d-on/14d-off

Single dose

(N = 4)

(N = 3)

(N = 4)

(N = 7)

(N = 4)

(N = 4)

(N = 6)

(N = 6)

(N = 9)a

Cmax

(ng/mL)

215 (50.2)

250 (72.2)

743 (65.1)

972 (82.7)

1180 (24.7)

1209 (85.4)

2172 (16.3)

2555 (29.9)

3225 (35.5)

Tmax

(h)

0.65 (0.40, 0.97)

0.88 (0.42, 0.93)

0.49 (0.43, 1.03)

0.95 (0.37, 3.80)

0.69 (0.37, 0.90)

0.96 (0.47, 1.92)

0.68 (0.48, 2.00)

0.50 (0.50, 1.10)

0.58 (0.45, 1.12)

AUC0-12

(h*ng/mL)

690 (51.3)

819 (99.0)

2551 (107.3)

4250 (50.4)

4147 (30.3)

5100 (57.9)

7028 (10.9)

7455 (27.3)

10074 (42.0)

AUC0-t

(h*ng/mL)

754 (58.4)

852 (111.3)

2802 (123.7)

4895 (48.2)

4561 (35.3)

5858 (50.2)

7831 (17.8)

8240 (27.9)

11119 (45.5)

AUC0-inf

(h*ng/mL)

769 (58.3)

864 (110.5)

2825 (123.9)

4926 (47.8)

4603 (35.2)

5906 (49.3)

7870 (17.9)

8284 (28.1)

11164 (45.4)

t1/2

(h)

4.42 (82.9)

3.11 (106.3)

4.90 (115.1)

5.74 (37.6)

8.60 (103.8)b

5.93 (51.2)

5.51 (34.3)

7.45 (61.8)

6.37 (41.6)

Multiple dose

(N=3)

(N=3)

(N=3)

(N=7)

(N=3)

(N=2)

(N=6)

(N=5)

(N=7)c

Cmax (ng/mL)

165 (15.7)

291 (124.9)

676 (48.0)

1167 (87.9)

1599 (33.7)

1253 (7.3)

2303 (34.0)

2193 (29.1)

3034 (33.6)

Tmax (h)

0.88

(0.42, 0.95)

0.92

(0.90, 1.27)

0.93

(0.57, 1.08)

1.10

(0.47, 2.58)

0.88

(0.38, 1.00)

0.75

(0.50, 1.00)

1.88

(0.50, 2.00)

0.50

(0.50, 1.00)

0.50

(0.50, 2.05)

t1/2 (h)

2.67 (31.0)

2.25 (26.5)

2.55 (24.6)

4.09 (36.8)

2.45 (42.8)

3.53 (3.1)

2.59 (9.6)

2.92 (18.3)

3.01 (20.0)d

Cmin (ng/mL)

7.48 (208.2)

15.8 (212.1)

25.5 (137.3)

144 (107.2)

21.0 (2741.3)

91.4 (72.9)

129 (51.8)

115 (92.5)

164 (54.3)

AUCtau (h*ng/mL)

597 (61.1)

997 (168.9)

2056 (76.9)

5605 (76.6)

5144 (30.3)

4432 (43.6)

8189 (29.3)

7732 (46.8)

11353 (27.9)

Racc

1.02 (37.9)

1.22 (40.3)

1.15 (17.4)

1.32 (39.4)

1.18 (6.7)

1.26 (9.2)

1.17 (25.3)

1.04 (32.5)

1.18 (24.1)e

  1. The parameters are presented as the geometric mean (geometric CV), and Tmax is presented as the median (minimum, maximum)
  2. Abbreviations: Cmax maximum concentration, Tmax time to reach maximum concentration, AUC0-12 area under the curve from time zero to 12 h, AUC0-t area under the curve from time zero to the time of the last quantifiable concentration, AUC0-inf area under the curve from time zero to infinity, t1/2 elimination half-life, Cmin minimum concentration, AUCtau area under the curve over a dosing interval, Racc accumulation ratio calculated by AUC
  3. aThis cohort is only 85 mg BID 14d-on/14d-off in the dose escalation part. PK samples after a single administration were not collected in the dose expansion part
  4. bThe t1/2 of one subject in 40 mg BID 14d-on/14d-off was not reported due to R2 <0.75, n=3
  5. cThis cohort represents 85 mg BID 14d-on/14d-off in the dose escalation part combined with 85 mg BID 14d-on/14d-off in the dose expansion part
  6. dThe t1/2 of two subjects in 85 mg BID 14d-on/14d-off in the dose expansion part was not reported due to R2 <0.75, n=5
  7. ePK samples after a single administration were not collected in the dose expansion part. Therefore, the Racc of these two subjects cannot be calculated, n=5
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BMC Cancer

ISSN: 1471-2407

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