Table 1 |.
Selected ongoing clinical trials with ATR, CHK1 and WEE1 inhibitors according to strategy
| Design | Target | Agents | Indication | Status | Study Identifier |
|---|---|---|---|---|---|
| Biomarker driven monotherapy trials | |||||
| Phase II | CHK1 | Prexasertib | Advanced solid tumours with replication stress or homologous recombination deficiency | Active, not recruiting | NCT02873975 |
| Phase II | WEE1 | Adavosertib | Advanced refractory solid tumours | Suspended | NCT03253679 |
| Combination with chemotherapy | |||||
| Phase I | ATR | Gemcitabine, carboplatin and berzosertib | Platinum-sensitive ovarian cancer | Recruiting | NCT02627443 |
| Phase I | ATR | Gemcitabine and BAY1895344 | Incurable solid tumours; expansion cohort platinum-resistant ovarian cancer | Not yet recruiting | NCT04616534 |
| Phase I | WEE1 | Gemcitabine, nab-paclitaxel and adavosertib | Unresectable pancreatic adenocarcinoma | Active, not recruiting | NCT02194829 |
| PARPi synergism | |||||
| Phase II | ATR | Ceralasertib and olaparib | Recurrent HGSOC irrespective of platinum sensitivity | Recruiting | NCT03462342 (CAPRI trial) |
| Phase II | ATR | Ceralasertib, olaparib | Recurrent gynaecological cancers, including CCC and rare gynaecological cancer subtypes with frequent ARID1A loss | Recruiting | NCT04065269 (ATARI trial) |
| Phase II | ATR; WEE1 | Olaparib alone; olaparib and capivasertib; olaparib and ceralasertib; olaparib and adavosertib | Advanced solid tumours with positive predictive biomarkers | Not yet recruiting | NCT02576444 (OLPACO trial) |
| Randomized phase II | ATR | Ceralasertib, olaparib; placebo, olaparib | HGSOC relapsed after at least 6 months maintenance with PARPi | Recruiting | NCT04239014 (DUETTE trial) |
| Randomized phase II | ATR; WEE1 | Olaparib; ceralasertib and olaparib; adavosertib and olaparib | Metastatic triple-negative breast cancer | Active, not recruiting | NCT03330847 (VIOLETTE trial) |
| Phase I | ATR | BAY1895344 and niraparib | Advanced solid tumours and ovarian cancer; two expansion ovarian cancer cohorts: PARPi naive, PARPi resistant | Recruiting | NCT04267939 |
| Phase I | WEE1 | Olaparib, adavosertib | Advanced refractory solid tumour with mutations in DDR genes | Recruiting | NCT04197713 (STAR trial) |
| Phase I/II | ATR | Ceralasertib; ceralasertib and carboplatin; ceralasertib and olaparib; ceralasertib and durvalumab | Head and neck squamous cell carcinoma, non-small-cell lung carcinoma, gastric, breast and ovarian cancer | Recruiting | NCT02264678 |
| Overcoming PARPi resistance | |||||
| Phase I/II | ATR | Olaparib and ceralasertib | Platinum-sensitive ovarian cancer after PARPi progression | Recruiting | NCT02264678 |
| Phase I | ATR | Niraparib once daily plus M4344 100–200 mg daily | Patients with ovarian cancer with disease progression while on PARPi | Not yet recruiting | NCT04149145 |
| Phase I | CHK1 | Olaparib and prexasertib | Advanced solid tumours with prior PARPi treatment | Active, not recruiting | NCT03057145 |
| Phase II | WEE1 | Adavosertib; adavosertib and olaparib | Patients with ovarian cancer with disease progression while on PARPi | Recruiting | NCT03579316 |
| Immunotherapy combinations | |||||
| Phase I/II | ATR | Berzosertib and avelumab | Advanced solid tumours | Recruiting | NCT04266912 |
| Phase I | ATR | BAY1895344 and pembrolizumab | Advanced solid tumours | Recruiting | NCT04095273 |
ATR, ataxia telangiectasia mutated (ATM)- and Rad3-related; CCC, clear cell cancer; DDR, DNA damage response; HGSOC, high-grade serous ovarian cancer; PARPi, poly[ADP-ribose]polymerase 1 inhibitor.