Table 2

Selected clinical trials of cell cycle checkpoint inhibitors with PD-1/PD-L1 immune checkpoint blockade relevant to gynecological cancers

Drug	Phase	Population and treatment	Activity	Reference
ATR inhibitors
Berzosertib (M6620; VX-970)	Ib/II	Recurrent platinum-sensitive ovarian cancer that is resistant to PARPi Part A: Safety run-in of carboplatin (AUC 5 D1) + avelumab (1600 mg D1) + berzosertib (90 mg/m² D2), every 3 weeks. Dose de-escalations of berzosertib are allowed to 60 mg/m² or 40 mg/m² Part B: Patients are randomized to standard of care chemotherapy ± bevacizumab (carboplatin + paclitaxel/gemcitabine/pegylated liposomal doxorubicin ± bevacizumab) followed by maintenance bevacizumab, or the combination of carboplatin + avelumab + berzosertib for six cycles followed by avelumab maintenance until disease progression or intolerable toxicity	Recruitment completed, results awaited	NCT03704467
BAY1895344	Ib	Advanced solid tumors with dose expansion cohort in patients with DDR-deficiency biomarker positive gynecological cancers, gastric, breast, and prostate cancer Patients are treated with BAY1895344 + pembrolizumab	Recruitment ongoing	NCT04095273
CHK1/2 inhibitors
Prexasertib	I	Advanced solid tumors Patients are treated with prexasertib + LY3300054 (PD-L1 inhibitor)	Recruitment ongoing	NCT03495323
CDK inhibitors
Ribociclib	I	Advanced breast cancer or epithelial ovarian cancer Patients are treated with ribociclib + PDR001 (PD-1 inhibitor) ± fulvestrant	Recruitment ongoing	NCT03294694
DNA-PKcs inhibitors
Nedisertib; M3814	I	Advanced solid tumors, and who are amenable to radiotherapy Patients are treated with nedisertib + avelumab ± palliative radiotherapy	Recruitment ongoing	NCT03724890

ATR, ataxia telangiectasia and Rad3 related; AUC, area under curve; CDK, cyclin-dependent kinase; CHK1/2, checkpoint kinases 1 and 2; DNA-PKcs, DNA-dependent protein kinase catalytic subunits; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1.