Table A2.
Best responses across models based on ATM mutations.
| Median Best Response as % TGI (95% CI) | * p-Value | |||||||
|---|---|---|---|---|---|---|---|---|
| Treatment Group | Dose (mg/kg) and Schedule | ATM Truncating VAF > 0.5 (n = 5) A |
ATM Truncating VAF ≤ 0.5 (n = 3) B |
ATM Missense (n = 3) C |
ATM Truncating VAF ≤ 0.5 + Missense (n = 6) B + C |
A vs. B | A vs. C | A vs. B + C |
| AZD6738 | 25 BID 14ON 14OFF | 54 (27, 94) | 33 (23, 40) | 27 (−20, 60) | 30 (3, 46) | 0.03 | 0.03 | 0.009 |
| AZD6738 | 12.5 BID 14ON 14OFF | 46 (19, 73) | 29 (9, 43) | 35 (−74, 125) | 30 (−1, 53) | 0.3 | 0.4 | 0.2 |
| AZD7648 | 100 QD continuous | 43 (23, 56) | 51 (30, 77) | 25 (−163, 178) | 49 (−22, 84) | 0.1 | 0.8 | 0.5 |
| Olaparib | 100 QD continuous | 32 (20, 44) | 16 (−12, 56) | −4 (−197, 168) | 14 (−50, 58) | 0.3 | 0.6 | 0.3 |
| Olaparib | 100 BID continuous | 26 (2, 78) | 34 (−7, 83) | −5 (−188, 154) | 28 (−46, 68) | >0.99 | 0.3 | 0.4 |
| AZD6738 + olaparib | 12.5 BID 14ON 14OFF + 100 QD continuous | 59 (40, 104) | 47 (45, 49) | 59 (−43, 134) | 48 (23, 70) | 0.03 | 0.8 | 0.1 |
| AZD6738 + AZD7648 | 12.5 BID 14ON 14OFF + 100 QD continuous | 68 (33, 101) | 57 (11, 90) | 62 (−131, 197) | 59 (−5, 88) | 0.4 | 0.8 | 0.4 |
| AZD7648 + olaparib | 100 QD + 100 QD continuous | 44 (21, 82) | 64 (25, 94) | 50 (−93, 179) | 57 (12, 90) | 0.6 | >0.99 | 0.7 |
* p-value = non-parametric Mann–Whitney test, median best response % TGI compared between models with different ATM mutations for each treatment group, respectively. BID—twice-daily dosing, QD—once-daily dosing.