Combination therapy using durvalumab and histotripsy for treatment of intrahepatic cholangiocarcinoma (CODAH trial)

Sample size calculation

• Endpoint: PFS
• Power: 80%; type I error: 0.05
• Durva: median PFS 7.2 months
• Test: one-sample, one-sided test for PFS in combination therapy [durva + histo] > 7.2 months
• Follow-up: patient accrual over a 24 months with at least 1 year follow-up after last patient accrued

Number of patients in combination therapy group

Median PFS in [durva + histo]	Number of patients
9.0	127
9.1	115
9.2	105
9.3	96
9.4	89
9.5	82
9.6	76
9.7	71
9.8	66
9.9	62
10.0	58
10.1	55
10.2	52
10.3	49
10.4	47
10.5	44
10.6	42
10.7	40
10.8	38
10.9	37
11.0	35
11.1	34
11.2	32
11.3	31
11.4	30
11.5	29
11.6	28
11.7	27
11.8	26
11.9	25
12.0	24
12.1	23
12.2	23
12.3	22
12.4	21
12.5	21
12.6	20
12.7	20
12.8	19
12.9	19
13.0	18
13.1	18
13.2	17
13.3	17
13.4	16
13.5	16
13.6	16
13.7	15
13.8	15
13.9	15
14.0	14
14.1	14
14.2	14
14.3	13
14.4	13
14.5	13
14.6	13
14.7	12
14.8	12
14.9	12
15.0	12

Immune AE

In Topaz-I the rate of immune-mediated adverse events was 12.7% with durvalumab.

• Non-inferiority

Number of patients in combination therapy group

AE rate in [durva + histo]	Number of patients
0.170	374
0.175	301
0.180	247
0.185	207
0.190	176
0.195	151
0.200	132
0.205	116
0.210	103
0.215	92
0.220	82
0.225	74
0.230	67
0.235	62
0.240	56
0.245	52
0.250	48