Table 1.
Clinical trials of ATR inhibitors.
| Trial Phase |
Disease Setting |
Treatments | Most Common Grade ≥ 3 Toxicity |
Efficacy | Reference |
|---|---|---|---|---|---|
| Berzosertib/M6620/VX-970 | |||||
| 1 | Solid tumors | Escalating doses of M6620 with topotecan |
Anemia (19%), Leukopenia (19%), Neutropenia (19%) |
PR 2/21 (10%) SD 7/21 (33%) |
[51] |
| 1 | Solid tumors | Escalating doses of M6620, or combination with carboplatin |
Monotherapy: None With carboplatin: Neutropenia (22%) |
Monotherapy: PR 1/17 (6%) SD 5/17 (29%) With carboplatin: PR 1/21 (5%) SD 15/21 (71%) |
[52] |
| 1 | Solid tumors | Escalating doses of berzosertib with cisplatin | Neutropenia (20%), Anemia (17%) |
PR 4/26 (15%) SD 15/26 (58%) |
[53] |
| 1 | Solid tumors | Escalating doses of berzosertib with gemcitabine +/− cisplatin | With gemcitabine Neutropenia (16%) ALT increased (16%) Fatigue (16%) With gemcitabine + cisplatin Neutropenia (63%) Thrombocytopenia (38%) |
With gemcitabine PR 4/48 (8%) SD 29/48 (60%) With gemcitabine + cisplatin PR 1/7 (14%) SD 4/7 (57%) |
[54] |
| 2 | Ovarian cancer (Platinum-resistant) |
Randomization (1:1) Gemcitabine +/− berzosertib | Gemcitabine + berzosertib: Neutropenia (35%) Anemia (15%) Gemcitabine alone: Neutropenia (28%) Anemia (11%) |
Gemcitabine + berzosertib PFS 22.9 weeks Gemcitabine alone PFS 14.7 weeks (HR 0.57, 90% CI 0.33–0.98) |
[55] |
| 2 | Urothelial carcinoma | Randomization (1:1) Gemcitabine + Cisplatin +/− berzosertib | Gemcitabine + cisplatin + berzosertib: Anemia (57%) Gemcitabine + cisplatin: Anemia (25%) |
Gemcitabine + cisplatin + berzosertib: PFS 8.0 months OS 14.4 months Gemcitabine + cisplatin: PFS 8.0 months OS 19.8 months HR for PFS: 1.22 (95% CI 0.72–2.08) HR for OS: 1.42 (95% CI 0.76–2.68) |
[56] |
| Ceralasertib/AZD6738 | |||||
| 1 | Solid tumors | Escalating doses of berzosertib with paclitaxel | Neutropenia (30%) Anemia (23%) |
CR 1/57 (2%) PR 12/57 (21%) SD 18/57 (32%) |
[59] |
| 1 | Solid tumors | Escalating doses of berzosertib with carboplatin | Anemia (39%) Thrombocytopenia (36%) Neutropenia (25%) |
PR 2/34 (6%) SD 18/34 (53%) |
[60] |
| 2 | Melanoma | Ceralasertib + Durvalumab | Anemia (33%) Thrombocytopenia (23%) |
PR 9/30 (30%) SD 10/30 (33%) Median PFS 7.1 months (95% CI 3.6–10.6) Median OS 14.2 months (95% CI 9.3–19.1) |
[65] |
| BAY-1895344 | |||||
| 1 | Solid tumors | Escalating doses of BAY-1895344 | Neutropenia (55%) Leukopenia (18%) Thrombocytopenia (18%) |
PR 4/21 (19%) SD 8/21 (38%) |
[63] |
| M4344 | |||||
| 1 | Solid tumors | Escalating doses of M4344 or combination with carboplatin |
Trial ongoing (Not reported) |
Trial ongoing (Not reported) |
NCT 02278250 |
PR, partial response; SD, stable disease; PFS, progression-free survival; OS, overall survival.