Table 2.
AEs (safety analysis set)
| Part B: osimertinib 80 mg + savolitinib 600/300 mg | Part D: osimertinib 80 mg + savolitinib 300 mg | ||||
|---|---|---|---|---|---|
| B1. Previously received 3G EGFR-TKI | B2. No prior 3G EGFR-TKI, T790M-negative | B3. No prior 3G EGFR-TKI, T790M-positive | All patients | No prior 3G EGFR-TKI, T790M-negative | |
| Patients with an event, n (%) | n = 69 | n = 51 | n = 18 | (N = 138)a | (n = 42) |
| Any AE | 69 (100) | 51 (100) | 18 (100) | 138 (100) | 41 (98) |
| Any AE grade ≥3 | 39 (57) | 35 (69) | 12 (67) | 86 (62) | 21 (50) |
| Possibly causally related to: | |||||
| Osimertinib only | 3 (4) | 3 (6) | 2 (11) | 8 (6) | 2 (5) |
| Savolitinib only | 14 (20) | 13 (25) | 7 (39) | 34 (25) | 5 (12) |
| Osimertinib and savolitinib | 11 (16) | 17 (33) | 9 (50) | 37 (27) | 7 (17) |
| Any AE leading to death | 3 (4) | 3 (6) | 1 (6) | 7 (5) | 2 (5) |
| Any AE leading to discontinuation | |||||
| Osimertinib | 12 (17) | 9 (18) | 3 (17) | 24 (17) | 8 (19) |
| Savolitinib | 19 (28) | 20 (39) | 10 (56) | 49 (36) | 15 (36) |
| AE leading to discontinuation, possibly causally related to any treatment | |||||
| Osimertinib | 8 (12) | 6 (12) | 1 (6) | 15 (11) | 5 (12) |
| Savolitinib | 15 (22) | 17 (33) | 6 (33) | 38 (28) | 12 (29) |
| Any AE leading to interruption or reduction | |||||
| Osimertinib | 22 (32) | 25 (49) | 12 (67) | 59 (43) | 13 (31) |
| Savolitinib | 27 (39) | 25 (49) | 9 (50) | 61 (44) | 16 (38) |
| Any SAEb | 33 (48) | 27 (53) | 7 (39) | 67 (49) | 16 (38) |
| Possibly causally related to: | |||||
| Osimertinib only | 0 | 0 | 0 | 0 | 1 (2) |
| Savolitinib only | 6 (9) | 6 (12) | 3 (17) | 15 (11) | 2 (5) |
| Osimertinib and savolitinib | 5 (7) | 7 (14) | 2 (11) | 14 (10) | 4 (10) |
| Any SAE leading to discontinuation | |||||
| Osimertinib | 9 (13) | 8 (16) | 3 (17) | 20 (14) | 2 (5) |
| Savolitinib | 11 (16) | 11 (22) | 6 (33) | 28 (20) | 6 (14) |
| Any SAE leading to interruption or reduction | |||||
| Osimertinib | 10 (14) | 11 (22) | 6 (33) | 27 (20) | 10 (24) |
| Savolitinib | 9 (13) | 9 (18) | 2 (11) | 20 (14) | 7 (17) |
NOTE: Causality determined by investigator review.
Abbreviations: SAE, serious adverse event; 3G, third-generation.
aMost patients were enrolled to 600 mg savolitinib, prior to weight-based dosing implementation, but, following a protocol amendment, the final 21 patients enrolled in Part B were dosed with savolitinib by body weight as follows: patients who weighed ≤55 kg (n = 7) received 300 mg q.d., and those weighing >55 kg (n = 14) received 600 mg q.d.
bIncluding events leading to death.