Table 2.
Clinical Trials of DDR inhibitors in CRC patients.
| Inhibitor | NCT Number | Conditions | Primary and Secondary Endpoints | Intervention/Treatment for CRC | Phase(s) | Status | Reference | |
|---|---|---|---|---|---|---|---|---|
| Chk1 Inhibitor | Prexasertib (LY2606368) | NCT02860780 | Advanced/metastatic cancer, including CRC with KRAS and/or BRAF mutations | MTD | Prexasertib + ralimetinib | Phase 1 | Completed | [250] |
| NCT02124148 | Advanced/metastatic cancer, including KRAS wild type CRC, which has failed to oxaliplatin- and irinotecan-based chemotherapy or is intolerant of irinotecan or oxaliplatin | Prexasertib + cetuximab | Phase 1b | Completed | - | |||
| LY2880070 | NCT02632448 | Solid tumors, including CRC | MTD | LY2880070 ± gemcitabine | Phase 1b/2a | Recruiting | [251] | |
| SRA737 | NCT02797964 | Advanced solid tumors (including CRC) and non-Hodgkin’s lymphoma | Subjects with TRAE, MTD, recommended Phase 2 dose, ORR | SRA737 | Phase 1/2 | Completed | [252] | |
| ATM Inhibitor | AZD0156 | NCT02588105 | Advanced solid tumors, including CRC | Subjects with TRAE | AZD0156 + irinotecan/ FOLFIRI |
Phase 1 | Active, not recruiting | [253] |
| ATR Inhibitor | Ceralasertib (AZD6738) | NCT04704661 | Advanced solid tumors, including CRC that have a change (mutation) in the HER2 gene or protein | RP2D, PD profile of tumor tissues between Top1 inhibition and Top1 + ATR dual inhibition | Ceralasertib + trastuzumab deruxtecan | Phase1/1b | Not yet recruiting | - |
| Elimusertib (BAY 1895344) | NCT04535401 | Advanced or metastatic cancers of the stomach and intestines, including CRC, which have previously progressed on irinotecan with and without DDR defects | MTD | Elimusertib + FOLFIRI | Phase 1 | Not yet recruiting | [254] | |
| Berzosertib (M6620, VX-970) | NCT02157792 | Advanced solid tumors, including CRC harboring molecular aberrations, including ATM loss and an ARID1A mutation, achieved complete response, and maintained this response, with a progression-free survival of 29 months at last assessment | Safety (AE, laboratory values, ECG), ORR | M6620 + carboplatin | Phase 1 | Completed | [255,256] | |
| WEE1 inhibitor | Adavosertib (AZD1775, MK-1755) | NCT02906059 | Metastatic CRC with RAS (KRAS or NRAS) or BRAF mutated | DLT and TREA | AZD1775 + irinotecan | Phase Ib | Completed | [257] |
| NCT02465060 | Advanced refractory solid tumors (including CRC), lymphomas, or multiple myeloma | ORR | Adavosertib + targeted therapy according to mutational status | Phase II | Recruiting | [258,259] | ||
| NCT00648648 | Advanced solid tumors, including CRC | DLT, best ORR | Adavosertib + gemcitabine + cisplatin or carboplatin | Phase 1 | Completed | [260] | ||
| ZN-c3 | NCT04158336 | Solid tumors, including CRC | MTD, RP2D, DLR, ORR | ZN-c3 | Phase I/II | Recruiting | [261] | |
CRC, colorectal cancer; MTD: maximum tolerated dose; TRAE: treatment-related adverse event; RP2D: recommended phase 2 dose; ORR: objective response rate; PD: pharmacodynamics; ECG: electrocardiogram; SD: stable disease, DLT: dose limiting toxicities; pCR: pathological clinical response; cCR: clinical complete response; PR: pathological response.