Table 3.
Recent clinical trials for ATR, ATM, DNA-PK, CHK1, CHK2, WEE1, PKMYT1, CDKs, PLK1, POLQ, USP1, RAD51, WRN and APE1 inhibitors: monotherapy and combination therapy
| Target | Agent | Intervention | Cancer type | Phase | Clinicaltrials.gov identifier |
|---|---|---|---|---|---|
| ATR | Ceralasertib | Ceralasertib + Durvalumab vs Docetaxel | NSCLC | III | NCT05450692 |
| Ceralasertib + Durvalumab | NSCLC | III | NCT06732401 | ||
| Ceralasertib | Advanced solid tumors | IIA | NCT04564027 | ||
| Ceralasertib | NSCLC | II | NCT03334617 | ||
| Ceralasertib + Olaparib | Gynecologic cancer | II | NCT04065269 | ||
| Ceralasertib + Olaparib | NSCLC | II | NCT02937818 | ||
| Ceralasertib + Olaparib | SCLC | II | NCT03428607 | ||
| Ceralasertib + Olaparib | Ovarian cancer | II | NCT03462342 | ||
| Ceralasertib ± Olaparib | Breast cancer | II | NCT03182634 | ||
| Ceralasertib ± Olaparib | TNBC | II | NCT03330847 | ||
| Ceralasertib + Durvalumab | Melanoma | II | NCT03780608 | ||
| Ceralasertib + Acalabrutinib | CLL | I/II | NCT03328273 | ||
|
Ceralasertib ± Olaparib/ Durvalumab/Saruparib/Carboplatin |
Advanced solid tumors | I/II | NCT02264678 | ||
| Berzosertib | Berzosertib + Topotecan | SCLC | II | NCT03896503 | |
| Berzosertib + Topotecan | SCLC | II | NCT04768296 | ||
| Berzosertib + Sacituzumab govitecan | SCLC, extra-pulmonary small cell neuroendocrine cancer and PARPi resistant HRD-cancers | II | NCT04826341 | ||
| Cisplatin + Gemcitabine ± Berzosertib | Urothelial cancer | II | NCT02567409 | ||
| Gemcitabine ± Berzosertib | Ovarian, primary peritoneal or fallopian tube cancer | II | NCT02595892 | ||
| Gemcitabine ± Berzosertib | Leiomyosarcoma | II | NCT04807816 | ||
| Berzosertib + Irinotecan | TP53-mutant gastric or gastroesophageal junction cancer | II | NCT03641313 | ||
| Berzosertib + Carboplatin + Docetaxel | Prostate cancer | II | NCT03517969 | ||
| Berzosertib + Avelumab | Advanced solid tumors | II | NCT04266912 | ||
| Pembrolizumab + Gemcitabine + Carboplatin ± Berzosertib | NSCLC | I/II | NCT04216316 | ||
| Berzosertib + Lurbinectedin | SCLC and high-grade neuroendocrine cancers | I/II | NCT04802174 | ||
| Berzosertib + Topotecan | SCLC and extrapulmonary small cell cancers | I/II | NCT02487095 | ||
| Elimusertib | Elimusertib | Advanced solid tumors | I/II | NCT05071209 | |
| Elimusertib | Advanced solid tumors and lymphoma | I | NCT03188965 | ||
| Elimusertib + SOC CTx | Advanced solid tumors | I | NCT04491942NCT04616534NCT04514497 | ||
| Elimusertib + FOLFIRI CTx | Advanced cancers of the stomach and intestines | I | NCT04535401 | ||
| Elimusertib + Niraparib | Ovarian cancer and solid tumors (excluding prostate) | I | NCT04267939 | ||
| Elimusertib + Pembrolizumab | Advanced solid tumors | I | NCT04095273 | ||
| Elimusertib + Pembrolizumab | HNSCC | I | NCT04576091 | ||
| Camonsertib | Camonsertib | Solid tumors with ATM and SETD2 LOF | II | NCT04589845 | |
| Lunresertib + Camonsertib | Advanced cancer | II | NCT05605509 | ||
| Lunresertib + Camonsertib | CDK4/ 6i resistant ER+/ HER2- breast cancer | II | NCT05601440 | ||
| Camonsertib ± Talazoparib/Gemcitabine | Advanced solid tumors | I/II | NCT04497116 | ||
| Atezolizumab + Camonsertib ± Bevacizumab | NSCLC | I/II | NCT03337698 | ||
| Gartisertib | Gartisertib + Carboplatin | Advanced solid tumors | I | NCT02278250 | |
| Tuvusertib | Tuvusertib | SPOP-mutant prostate cancer | II | NCT05828082 | |
| Tuvusertib + Avelumab | Merkel cell skin cancer | II | NCT05947500 | ||
| Tuvusertib ± Avelumab | ARID1A-mutated endometrial cancer | II | NCT06518564 | ||
| Tuvusertib + Cemiplimab | NSCLC | II | NCT05882734 | ||
| Tuvusertib + Niraparib/Lartesertib | Ovarian cancer | II | NCT06433219 | ||
| Tuvusertib + Temozolomide | Advanced solid tumors and hematologic malignancies | I/II | NCT05691491 | ||
| ART0380 | ART0380 | Advanced solid tumors | II | NCT05798611 | |
| ART0380 ± Gemcitabine ± Irinotecan | Advanced solid tumors | I/II | NCT04657068 | ||
| SC0245 | SC0245 + Irinotecan | SCLC | II | NCT05731518 | |
| ATM | AZD0156 | AZD0156 + Olaparib/Irinotecan/ Fluorouracil/Folinic Acid | Advanced solid tumors | I | NCT02588105 |
| AZD1390 | AZD1390 + RT | Brain cancer | I | NCT03423628 | |
| AZD1390 + RT ± Durvalumab | Soft tissue sarcoma | I | NCT05116254 | ||
| AZD1390 + SBRT | Advanced solid tumor | I | NCT05678010 | ||
| AZD1390 + RT | NSCLC | I | NCT04550104 | ||
| AZD1390 | Healthy volunteers | I | NCT03215381 | ||
| WSD0628 | WSD0628 + RT | Glioblastoma | I | NCT05917145 | |
| Lartesertib | Tuvusertib + Niraparib/Lartesertib | Ovarian cancer | II | NCT06433219 | |
| Lartesertib | Advanced solid tumors | I | NCT04882917 | ||
| Tuvusertib + Lartesertib/Avelumab | Advanced solid tumors | I | NCT05396833 | ||
| ATM/ DNA-PK | XRD-0394 | XRD-0394 + RT | Advanced solid tumors | I | NCT05002140 |
| DNA-PK | CC-115 | CC-115 | Advanced solid tumors | I | NCT01353625 |
| CC-115 + Enzalutamide | Prostate cancer | I | NCT02833883 | ||
| CC-115 + Temozolmide | Glioblastoma | II | NCT02977780 | ||
| Peposertib | Peposertib + RT | Pancreatic cancer | I/II | NCT04172532 | |
| Peposertib + Avelumab + RT | Advanced solid tumors and hepatobiliary malignancies | I/II | NCT04068194 | ||
| Peposertib + RT ± Avelumab | CRPC | I/II | NCT04071236 | ||
| Peposertib + Capecitabine | Rectal cancer | I/II | NCT03770689 | ||
| Peposertib + Avelumab + Temozolomide | Pediatric cancer | I/II | NCT02813135 | ||
| AZD7648 | AZD7648 + Doxorubicin | Advanced solid tumors | I/IIA | NCT03907969 | |
| M9831 | VX-984 | Advanced solid tumors | I | NCT02644278 | |
| BY101298 | BY101298 | Advanced solid tumors | I | NCT06462716 | |
| DNA-PK/ mTor | Samotolisib | Samotolisib | Pediatric TSC1/2 or PI3K/ MTOR-mutated advanced solid tumors, NHL or histiocytic disorders | II | NCT03213678NCT03155620 |
| CHK1 | Prexasertib | Prexasertib + Irinotecan | Desmoplastic small round cell tumor and rhabdomyosarcoma | I/II | NCT04095221 |
| Prexasetib | Ovarian cancer, endometrial adenocarcinoma and urothelial carcinoma | I/II | NCT05548296 | ||
| Prexasertib | SCLC | II | NCT02735980 | ||
| Prexasertib | Breast, ovarian and prostate cancer | II | NCT02203513 | ||
| Prexasertib | HRD-solid tumors or solid tumors with replicative stress | II | NCT02873975 | ||
| Prexasertib | Ovarian cancer | II | NCT03414047 | ||
| Prexasertib + low dose Gemcitabine | HNSCC | II | NCT06597565 | ||
| Prexasertib + LY3023414 | TNBC | II | NCT04032080 | ||
| SRA737 | SRA737 | Advanced solid tumors or NHL | I/II | NCT02797964 | |
| SRA737 + Gemcitabine + Cisplatin | Advanced solid tumors | I/II | NCT02797977 | ||
| BBI-355 | BBI-355 ± Erlotinib/Futibatinib | EGFR- and FGFR2- amplificated tumors | I | NCT05827614 | |
| LY2880070 | LY2880070 ± Gemcitabine | Ewing sarcoma | I | NCT05275426 | |
| LY2880070 + Gemcitabine | Advanced or metastatic solid tumors | I | NCT02632448 | ||
| PEP07 | PEP07 | Advanced or metastatic solid tumors | I | NCT05983523 | |
| PEP07 | AML and mantle cell lymphoma | I | NCT05659732 | ||
| SMP-3124LP | SMP-3124LP | Advanced solid tumors | I/II | NCT06526819 | |
| CHK2 | PHI-101 | PHI-101 | Ovarian cancer | IA | NCT04678102 |
| PHI-101 | AML | I | NCT04842370 | ||
| WEE1 | Adavosertib | Adavosertib | SETD2-amplificated advanced solid tumors | II | NCT03284385 |
| Adavosertib | CCNE1-amplificated advanced solid tumors | II | NCT03253679 | ||
| Adavosertib | BRCA1/2m advanced solid tumors and hematologic malignancies | II | NCT04439227 | ||
| Adavosertib | Uterine serous carcinoma or carcinosarcoma | II | NCT03668340 | ||
| Adavosertib | Uterine serous carcinoma | II | NCT04590248 | ||
| Adavosertib | Prostate cancer | II | NCT03385655 | ||
| Adavosertib | SCLC | II | NCT02593019 | ||
| Adavosertib | BRCA1/2m advanced solid tumors and hematologic malignancies | II | NCT02465060 | ||
| Adavosertib + Carboplatin | Advanced solid tumors | II | NCT01827384 | ||
| Adavosertib + Carboplatin | SCLC | II | NCT02937818 | ||
| Adavosertib + Carboplatin | TP53-mutated ovarian cancer | II | NCT01164995 | ||
| Adavosertib + Carboplatin + Paclitaxel | Squamous cell lung cancer | II | NCT02513563 | ||
| Carbolatin + Paclitaxel ± Adavosertib | TP53-mutated ovarian cancer | II | NCT01357161 | ||
| Adavosertib + Cisplatin | Breast cancer | II | NCT03012477 | ||
| Adavosertib + Gemcitabine/Paclitaxel/ Carboplatin/Doxorubicin | Ovarian, primary peritoneal and fallopian tube cancer | II | NCT02272790 | ||
| Adavosertib + Paclitaxel | TP53-mutated gastric adenocarcinoma | II | NCT02448329 | ||
| Gemcitabine ± Adavosertib | Ovarian, primary peritoneal and fallopian tube cancer | II | NCT02101775 | ||
| Cytarabine ± Adavosertib | AML and myelodysplastic syndrome | II | NCT02666950 | ||
| Adavosertib + Gemcitabine + RT | Pancreatic adenocarcinoma | II | NCT02037230 | ||
| Adavosertib ± Olaparib | Ovarian, primary peritoneal and fallopian tube cancer | II | NCT03579316 | ||
| Olaparib ± Adavosertib | TNBC | II | NCT03330847 | ||
| Adavosertib + Paclitaxel + Gemcitabine | Pancreatic cancer | I/II | NCT02194829 | ||
| Adavosertib + Irinotecan | Advanced solid tumors | I/II | NCT02095132 | ||
| Adavosertib + Carboplatin | Relapsed or refractory pediatric cancer | I/II | NCT02813135 | ||
| Azenosertib | Azenosertib | Ovarian, primary peritoneal and fallopian tube cancer | II | NCT05128825 | |
| Azenosertib | Uterine serous carcinoma | II | NCT06369155NCT04814108 | ||
| Azenosertib + Gemcitabine | Pancreatic cancer | II | NCT06015659 | ||
| Azenosertib + Gemcitabine | Osteosarcoma | I/II | NCT04833582 | ||
| Azenosertib + Carboplatin + Pembrolizumab | TNBC | I/II | NCT06351332 | ||
| Debio-0123 | Debio-0123 + Sacituzumab govitecan | TNBC and HR+/ HER2- advanced breast cancer | I/II | NCT06612203 | |
| Debio-0123 + Temozolomide + RT | Glioblastoma and astrocytoma | I/II | NCT05765812 | ||
| Potrasertib | IMP7068 | Advanced solid tumors | I | NCT04768868 | |
| SY-4835 | SY-4835 | Advanced solid tumors | I | NCT05291182 | |
| APR-1051 | APR-1051 | Advanced solid tumors | I | NCT06260514 | |
|
WEE1/ PKMYT1 |
ACR-2316 | ACR-2316 | Advanced solid tumors | I | NCT06667141 |
| PKMYT1 | Lunresertib | Lunresertib + Gemcitabine/Camonsertib | CDK4/ 6i resistant ER+/ HER2- breast cancer | II | NCT05601440 |
| Lunresertib + Gemcitabine/FOLFIRI/Trastuzumab/Camonsertib | TP53/FBXW7/PPP2R1A/KRAS-mutated or CCNE1-amplified advanced cancer | II | NCT05605509 | ||
| Lunresertib + Carboplatin + Paclitaxel | Recurrent TP53-mutated ovarian and uterine cancer | I | NCT06107868 | ||
| Lunresertib + XELOX | CCNE1-amplificated and FBXW7-mutant advanced gastrointestinal cancer | I | NCT05147350 | ||
| Lunresertib ± Camonsertib/Debio-0123 | Advanced solid tumors | I | NCT04855656 | ||
| CDK4/6 | Palbociclib | Palbociclib + Fulvestrant | HR+/HER2- breast cancer | III | NCT01942135 |
| Palbociclib | Chordoma with CDKN2A/B LOF or RB1-/CDK4/6-positive | II | NCT03110744 | ||
| Palbociclib | Advanced cancer with CDKN2A/B LOF or CDK4/6 amplifications | II | NCT02693535 | ||
| Palbociclib | RB1-positive anaplastic oligodendroglioma | II | NCT02530320 | ||
| Abemaciclib | Abemaciclib | RB1-positive TNBC | II | NCT03130439 | |
| Abemaciclib | Thyroid cancer | II | NCT04552769 | ||
| Abemaciclib | CDKN2A-deficient mesothelioma | II | NCT03654833 | ||
| Abemaciclib ± Samotolisib ± Gemcitabine/Capecitabine | Pancreatic ductal adenocarcinoma | II | NCT02981342 | ||
| Abemaciclib + Samotolisib + Fulvestrant vs Other | Metastatic breast cancer | IB | NCT02057133 | ||
| CDK2 | INCB123667 | INCB123667 vs CTx | PtR ovarian cancer with cyclin E1 overexpression | III | NCT07214779 |
| INCB123667 | PtR ovarian cancer with cyclin E1 overexpression | II | NCT07023627 | ||
| INCB123667 ± Palbociclib/Ribociclib±Fulvestrant/ Bevacizumab/Olaparib/Paclitaxel | Advanced solid tumors | I | NCT05238922 | ||
| PLK1 | Onvansertib | Onvansertib | Relapsed SCLC with TP53-mutation and YAP1- or MYC expression | II | NCT05450965 |
| Onvansertib ± FOLFIRI/FOLFOX+Bevacizumab | KRAS/NRAS-mutated mCRC (first line) | II | NCT06106308 | ||
| Onvansertib + FOLFIRI + Bevacizumab | KRAS-mutated mCRC (second line) | I | NCT03829410 | ||
| POLQ | ART4215 | ART4215 ± Talazoparib | Advanced solid tumors | I/IIA | NCT04991480 |
| ART6043 | ART6043 ± Olaparib/Niraparib | Advanced solid tumors | I/IIA | NCT05898399 | |
| GSK4524101 | GSK4524101 ± Niraparib | Solid tumors | I/II | NCT06077877 | |
| RP-3467 | RP-3467 ± Olaparib | Advanced solid tumors | I | NCT06560632 | |
| SYN818 | SYN818 | Advanced solid tumors | I | NCT06666270 | |
| Novobiocin | Novobiocin | Advanced solid tumors | I | NCT05687110 | |
| USP1 | KSQ-4279 | KSQ-4279 ± PARPi | Advanced solid tumors | I | NCT05240898 |
| XL309 | XL309 ± Olaparib | Advanced solid tumors | I | NCT05932862 | |
| RAD51 | Emzadirib | Emzadirib ± Gemcitabine/Capecitabine/ Rituximab and Bendamustine | B-cell malignancies and advanced solid tumors | I/II | NCT03997968 |
| WRN | GSK4418959 | GSK4418959 ± PD-1 inhibitor | MSI-H or MMR-deficient advanced solid tumors | I/II | NCT06710847 |
| HRO761 | HRO761 ± Pembrolizumab/Irinotecan | MSI-H or MMR-deficient advanced solid tumors | I | NCT05838768 | |
| RO7589831 | RO7589831 ± Pembrolizumab | MSI-H or MMR-deficient advanced solid tumors | I | NCT06004245 | |
| APE1 | APX3330 | APX3330 | Advanced solid tumors | I | NCT03375086 |
| TRC102 | TRC102 + Pemetrexed + Cisplatin | Advanced solid tumors or mesothelioma | I/II | NCT02535312 | |
| TRC102 + Temozolomide | Solid tumors and lymphomas | I/II | NCT01851369 |
Data extracted from clinicaltrials.gov up until November 2025