Table 3.
Clinical trials of CHK1/2 inhibitors.
| Trial Phase |
Disease Setting |
Treatments | Most Common Grade ≥ 3 Toxicity |
Efficacy | Reference |
|---|---|---|---|---|---|
| Prexasertib/LY2606368 | |||||
| 1 | Solid tumors | Escalating doses of LY2606368 | Neutropenia (89%) Leukopenia (71%) Anemia (69%) |
PR 2/45 (4%) SD 15/45 (33%) |
[93] |
| 1 | Solid tumors | Prexasertib monotherapy | Neutropenia (83%) Leukopenia (75%) Thrombocytopenia (33%) |
SD 8/11 (73%) | [94] |
| 1 | Solid tumors | Prexasertib in combination with standard chemotherapy | Prexasertib + Cisplatin Neutropenia (67%) Prexasertib + Cetuximab Neutropenia (54%) Prexasertib + 5-FU Neutropenia (100%) |
Prexasertib + Cisplatin PR 8/63 (13%) Prexasertib + Cetuximab PR 7/31 (5%) Prexasertib + 5-FU PR 1/8 (13%) |
[98] |
| 1 | Solid tumors | Prexasertib in combination with olaparib | Neutropenia (79%) |
BRCA-mutant HGSOC PR 4/18 (22%) SD 6/18 (33%) |
[99] |
| 1 | Solid tumors | Prexasertib in combination with LY3300054 (anti-PDL1 antibody) | Neutropenia (82%) Leukopenia (76%) |
PR 3/17 (18%) SD 8/17 (47%) |
[100] |
| 2 | HGSOC (BRCA-wild type) |
Prexasertib monotherapy | Neutropenia (93%) Leukopenia (82%) |
PR 8/28 (29%) Median PFS 7.4 months (95% CI 2.1–9.4) |
[95] |
| 2 | TNBC (BRCA-wild type) |
Prexasertib monotherapy | Neutropenia (89%) Anemia (33%) |
PR 1/9 (11%) SD 4/9 (44%) |
[96] |
| 2 | Small-cell lung cancer | Prexasertib monotherapy | Neutropenia (65%) | Platinum-sensitive: PR 3/58 (5%) SD 15/58 (26%) Platinum-refractory: PR 0/60 (0%) SD 12/60 (20%) |
[97] |
PR, partial response; SD, stable disease; HGSOC, high-grade serous ovarian cancer; TNBC, triple-negative breast cancer.