Table A4.
Comparison of best response between monotherapy and combination.
| Treatment Group | Dose (mg/kg) and Schedule | Mean % TGI ± SEM | * p-Value Combo vs. Mono | ||
|---|---|---|---|---|---|
| ATM IHC H Score < 5 (n = 8) |
ATM IHC H Score > 5 (n = 3) |
ATM IHC H Score < 5 |
ATM IHC H Score > 5 |
||
| AZD6738 | 25 BID 14ON 14OFF | 50 ± 9 | 18 ± 41 | NA | NA |
| AZD6738 | 12.5 BID 14ON 14OFF | 38 ± 7 | 25 ± 23 | NA | NA |
| AZD7648 | 100 QD continuous | 45 ± 5 | 8 ± 40 | NA | NA |
| Olaparib | 100 QD continuous | 28 ± 4 | −14 ± 42 | NA | NA |
| Olaparib | 100 BID continuous | 40 ± 9 | −17 ± 40 | NA | NA |
| AZD6738 + olaparib | 12.5 BID 14ON 14OFF + 100 QD continuous | 63 ± 8.3 | 46 ± 21 | vs. AZD6738: 0.001 vs. olaparib: 0.007 |
vs. AZD6738: 0.03 vs. olaparib: 0.1 |
| AZD6738 + AZD7648 | 12.5 BID 14ON 14OFF + 100 QD continuous | 61 ± 8.6 | 33 ± 38 | vs. AZD6738: 0.001 vs. AZD7648: 0.1 |
vs. AZD6738: 0.7 vs. AZD7648: 0.06 |
| AZD7648 + olaparib | 100 QD + 100 QD continuous | 54 ± 7.3 | 43 ± 32 | vs. AZD7648: 0.2 vs. olaparib: 0.03 |
vs. AZD7648: 0.06 vs. olaparib: 0.2 |
* p-value—paired t test, mean best response as % TGI compared between models with ATM IHC score < 5 and ATM IHC H score > 5 for each treatment group, respectively. Comparison conducted at equivalent doses of each compound between combination and respective monotherapy groups. BID—twice-daily dosing, QD—once-daily dosing, NA—not applicable.