Efficacy endpoints
| Endpoint . | Phase 1 part . | Phase 2 part (n = 35) . | All treated (n = 72) . | |||
|---|---|---|---|---|---|---|
| Dose escalation . | Dose expansion 1.8 mg/m2 (n = 13) . | |||||
| 1.2 mg/m2 (n = 3) . | 1.6 mg/m2 (n = 12) . | 1.8 mg/m2 (n = 9) . | ||||
| Hematologic remission, n (%) (95% CI)* | ||||||
| CR/CRi | 2 (67) (9-99) | 9 (75) (43-95) | 8 (89) (52-100) | 6 (46) (19-75) | 24 (69) (51-83)† | 49 (68) (56-79) |
| CR | 1 (33) | 7 (58) | 3 (33) | 2 (15) | 10 (29) | 23 (32) |
| CRi | 1 (33) | 2 (17) | 5 (56) | 4 (31) | 14 (40) | 26 (36) |
| Median (range) time to CR/CRi, d | 39 (22-56) | 29 (22-59) | 38 (22-78) | 27 (21-85) | 25.5 (15-91) | 27 (15-91) |
| Median (95% CI) DOR among responders,‡mo | ||||||
| CR/CRi | 4.7 (4.6-4.8) | NR (0.7-NR) | 10.8 (1.2-NR) | 7.2 (2.1-NR) | 3.8 (2.2-5.8)§ | 4.6 (3.8-6.6)‖ |
| CR | 4.6 | NR (0.7-NR) | 15.2 (1.2-15.2) | 6.1 (2.1-10.0) | 2.8 (0.9-5.5) | 4.6 (2.2-15.2) |
| CRi | 4.8 | NR (NR-NR) | 7.0 (1.7-NR) | NR (2.8-NR) | 4.0 (1.2-6.6) | 4.8 (3.8-9.0) |
| MRD negativity among responders,¶n (%) (95% CI) | ||||||
| CR/CRi | 2/2 (100) (16-100) | 8/9 (89) (52-100) | 8/8 (100) (63-100) | 5/6 (83) (36-100) | 18/24 (75) (53-90) | 41/49 (84) (70-93) |
| CR | 1/1 (100) (3-100) | 6/7 (86) (42-100) | 3/3 (100) (29-100) | 2/2 (100) (16-100) | 7/10 (70) (35-93) | 19/23 (83) (61-95) |
| CRi | 1/1 (100) (3-100) | 2/2 (100) (16-100) | 5/5 (100) (48-100) | 3/4 (75) (19-99) | 11/14 (79) (49-95) | 22/26 (85) (65-96) |
| Median (range) time to MRD negativity, d | 98.5 (98-99) | 32.0 (22-64) | 30.0 (22-141) | 25.0 (21-134) | 25.5 (21-80) | 29.0 (21-141) |
| HSCT rate | ||||||
| Patients proceeding to poststudy HSCT, n (%) | 0 | 9 (75) | 4 (44) | 3 (23) | 8 (23) | 24 (33) |
| Median (range) time to HSCT, d | — | 36 (20-60) | 61.5 (41-84) | 77 (55-90) | 40 (27-148) | 45.5 (20-148) |
| PFS‡ | ||||||
| Events, n (%) | 3 (100) | 6 (50) | 7 (78) | 11 (85) | 31 (89) | 58 (81) |
| Median (95% CI), mo | 5.5 (2.1-6.4) | 6.5 (1.4-NR) | 8.8 (1.3-16.7) | 1.9 (1.0-5.0) | 3.7 (2.6-4.7) | 3.9 (2.9-5.4) |
| Probability of PFS at 12 mo (95% CI) | 0 | 0.46 (0.20-0.70) | 0.44 (0.10-0.70) | 0.15 (0-0.40) | 0.08 (0-0.20) | 0.20 (0.10-0.30) |
| OS‡ | ||||||
| Events, n (%) | 3 (100) | 6 (50) | 6 (67) | 10 (77) | 29 (83) | 54 (75) |
| Median (95% CI), mo | 9.2 (2.1-11.3) | NR (2.6-NR) | 16.5 (2.6-NR) | 5.8 (3.5-10.8) | 6.4 (4.5-7.9) | 7.4 (5.7-9.2) |
| Probability of OS at 12 mo (95% CI) | 0 | 0.50 (0.20-0.70) | 0.67 (0.30-0.90) | 0.23 (0.10-0.50) | 0.18 (0.10-0.30) | 0.30 (0.20-0.40) |
| Endpoint . | Phase 1 part . | Phase 2 part (n = 35) . | All treated (n = 72) . | |||
|---|---|---|---|---|---|---|
| Dose escalation . | Dose expansion 1.8 mg/m2 (n = 13) . | |||||
| 1.2 mg/m2 (n = 3) . | 1.6 mg/m2 (n = 12) . | 1.8 mg/m2 (n = 9) . | ||||
| Hematologic remission, n (%) (95% CI)* | ||||||
| CR/CRi | 2 (67) (9-99) | 9 (75) (43-95) | 8 (89) (52-100) | 6 (46) (19-75) | 24 (69) (51-83)† | 49 (68) (56-79) |
| CR | 1 (33) | 7 (58) | 3 (33) | 2 (15) | 10 (29) | 23 (32) |
| CRi | 1 (33) | 2 (17) | 5 (56) | 4 (31) | 14 (40) | 26 (36) |
| Median (range) time to CR/CRi, d | 39 (22-56) | 29 (22-59) | 38 (22-78) | 27 (21-85) | 25.5 (15-91) | 27 (15-91) |
| Median (95% CI) DOR among responders,‡mo | ||||||
| CR/CRi | 4.7 (4.6-4.8) | NR (0.7-NR) | 10.8 (1.2-NR) | 7.2 (2.1-NR) | 3.8 (2.2-5.8)§ | 4.6 (3.8-6.6)‖ |
| CR | 4.6 | NR (0.7-NR) | 15.2 (1.2-15.2) | 6.1 (2.1-10.0) | 2.8 (0.9-5.5) | 4.6 (2.2-15.2) |
| CRi | 4.8 | NR (NR-NR) | 7.0 (1.7-NR) | NR (2.8-NR) | 4.0 (1.2-6.6) | 4.8 (3.8-9.0) |
| MRD negativity among responders,¶n (%) (95% CI) | ||||||
| CR/CRi | 2/2 (100) (16-100) | 8/9 (89) (52-100) | 8/8 (100) (63-100) | 5/6 (83) (36-100) | 18/24 (75) (53-90) | 41/49 (84) (70-93) |
| CR | 1/1 (100) (3-100) | 6/7 (86) (42-100) | 3/3 (100) (29-100) | 2/2 (100) (16-100) | 7/10 (70) (35-93) | 19/23 (83) (61-95) |
| CRi | 1/1 (100) (3-100) | 2/2 (100) (16-100) | 5/5 (100) (48-100) | 3/4 (75) (19-99) | 11/14 (79) (49-95) | 22/26 (85) (65-96) |
| Median (range) time to MRD negativity, d | 98.5 (98-99) | 32.0 (22-64) | 30.0 (22-141) | 25.0 (21-134) | 25.5 (21-80) | 29.0 (21-141) |
| HSCT rate | ||||||
| Patients proceeding to poststudy HSCT, n (%) | 0 | 9 (75) | 4 (44) | 3 (23) | 8 (23) | 24 (33) |
| Median (range) time to HSCT, d | — | 36 (20-60) | 61.5 (41-84) | 77 (55-90) | 40 (27-148) | 45.5 (20-148) |
| PFS‡ | ||||||
| Events, n (%) | 3 (100) | 6 (50) | 7 (78) | 11 (85) | 31 (89) | 58 (81) |
| Median (95% CI), mo | 5.5 (2.1-6.4) | 6.5 (1.4-NR) | 8.8 (1.3-16.7) | 1.9 (1.0-5.0) | 3.7 (2.6-4.7) | 3.9 (2.9-5.4) |
| Probability of PFS at 12 mo (95% CI) | 0 | 0.46 (0.20-0.70) | 0.44 (0.10-0.70) | 0.15 (0-0.40) | 0.08 (0-0.20) | 0.20 (0.10-0.30) |
| OS‡ | ||||||
| Events, n (%) | 3 (100) | 6 (50) | 6 (67) | 10 (77) | 29 (83) | 54 (75) |
| Median (95% CI), mo | 9.2 (2.1-11.3) | NR (2.6-NR) | 16.5 (2.6-NR) | 5.8 (3.5-10.8) | 6.4 (4.5-7.9) | 7.4 (5.7-9.2) |
| Probability of OS at 12 mo (95% CI) | 0 | 0.50 (0.20-0.70) | 0.67 (0.30-0.90) | 0.23 (0.10-0.50) | 0.18 (0.10-0.30) | 0.30 (0.20-0.40) |
NR, not reached.
95% CI is the exact CI for a binomial proportion.
One-sided P < .0001 for the null hypothesis (H0): CR + CRi rate ≤20% using binomial distribution.
Uncensored for HSCT.
Median DOR was similar upon inclusion of 4 additional patients censored for HSCT (3.8 [95% CI, 2.2-4.2] mo).
Median DOR was 4.3 (95% CI, 3.8-5.6) mo with 9 additional patients censored for HSCT.
MRD negativity was defined as <0.01% leukemic blasts/total nucleated mononuclear cells in BM; 95% CI is the exact CI for a binomial proportion.