TABLE 2.
Ongoing combination trials of DDR inhibitors with chemotherapy, radiotherapy, and target therapy
| Conditions | Interventions | Phase | Clinical trial* | |
|---|---|---|---|---|
| Chemotherapy | ||||
| PARP | ||||
| Cancer | Veliparib + VX‐970 + cisplatin | I | NCT02723864 | |
| Metastatic breast cancer | Veliparib + carboplatin/paclitaxel | III | NCT02163694 | |
| Ovarian, breast, pancreatic, prostate cancer | AZD5305 + Carboplatin/paclitaxe | I /II | NCT04644068 | |
| Ovarian cancer | Veliparib + carboplatin/paclitaxel | III | NCT02470585 | |
| Metastatic pancreatic adenocarcinoma | Veliparib + fluorouracil/irinotecan hydrochloride | II | NCT02890355 | |
| SCLC | Veliparib + topotecan | I | NCT03227016 | |
| Advanced solid tumors | IMP4297 + temozolomide | I | NCT04434482 | |
| Triple negative breast cancer, ovarian cancer | KU‐0059436 (AZD2281) + carboplatin/paclitaxel | I | NCT00516724 | |
| Breast cancer | ABT‐888 + temozolomide | II | NCT01009788 | |
| Metastatic BRCA‐associated breast cancer | Veliparib + cisplatin | II | NCT02595905 | |
| HR deficient advanced solid tumor malignancies | Niraparib + carboplatin | I | NCT03209401 | |
| Prostate carcinoma | Niraparib + chemotherapy | II | NCT04592237 | |
| Breast cancer | Olaparib + paclitaxel/carboplatin | II/III | NCT03150576 | |
| Adrenal gland pheochromocytoma, paraganglioma | Olaparib + temozolomide | II | NCT04394858 | |
| Advanced (stage IIIB‐C‐IV) ovarian, primary peritoneal and fallopian tube cancer | Rucaparib + paclitaxel/carboplatin | I /II | NCT03462212 | |
| BRCA‐mutated ovarian carcinoma | Olaparib + chemotherapy | I | NCT03943173 | |
| Gastric cancer | Olaparib + paclitaxel | II | NCT01063517 | |
| Ovarian cancer | Olaparib + carboplatin/paclitaxel | II | NCT01081951 | |
| Ovarian, fallopian tube, or primary peritoneal cancer | Rucaparib + chemotherapy | III | NCT02855944 | |
| Recurrent solid tumors and ewing sarcoma | Talazoparib + onivyde | I /II | NCT04901702 | |
| Uterine leiomyosarcoma | Olaparib + temozolomide | II | NCT03880019 | |
| Ovarian cancer | Talazoparib + chemotherapy | III | NCT03642132 | |
| Acute leukemia | Veliparib + temozolomide | I | NCT01139970 | |
| Recurrent ovarian carcinoma | Niraparib + chemotherapy + atezolizumab | III | NCT03598270 | |
| Metastatic malignant solid neoplasm | Veliparib + topotecan hydrochloride | I | NCT01012817 | |
| IDH1 mutation | BGB‐290 + temozolomide | I/II | NCT03914742 | |
| Recurrent glioma | Talazoparib + carboplatin | II | NCT04740190 | |
| Refractory lymphomas undergoing stem cell transplant | Olaparib + chemotherapy | I | NCT03259503 | |
| ATM | ||||
| Refractory cancer | AZD6738 + paclitaxel | I | NCT02630199 | |
| Advanced cancer | ART0380 + gemcitabine | I/II | NCT04657068 | |
| ATR | ||||
| Esophageal cancer | M6620 + cisplatin | I | NCT03641547 | |
| Advanced stage solid tumors | BAY 1895344 + chemotherapy | I | NCT04514497 | |
| Ovarian serous tumor | M6620 + gemcitabine | I | NCT02595892 | |
| NSCLC, SCLC | VX‐970 (M6620) + topotecan | I/II | NCT02487095 | |
| Cancer | AZD6738 + gemcitabine | I | NCT03669601 | |
| Metastatic malignant solid neoplasm | M6620 + irinotecan hydrochloride | I | NCT02595931 | |
| Refractory cancer | AZD6738 + paclitaxel | I | NCT02630199 | |
| Advanced solid tumors | BAY 1895344 + cisplatin | I | NCT04491942 | |
| Small cell cancers outside of the lungs | M6620 + topotecan | II | NCT03896503 | |
| CHK1 | ||||
| Brain tumor | LY2606368 + cyclophosphamide/gemcitabine | I | NCT04023669 | |
| WEE1 | ||||
| Metastatic pancreatic adenocarcinoma | MK‐1775 + paclitaxel/gemcitabine hydrochloride | I/II | NCT02194829 | |
| Ovarian, primary peritoneal, or fallopian tube cancer | MK‐1775 + paclitaxel/gemcitabine hydrochloride | II | NCT02101775 | |
| Radiotherapy | ||||
| PARP | ||||
| Triple negative breast cancer | Niraparib + radiation therapy/dostarlimab | II | NCT04837209 | |
| Triple negative breast cancer | Niraparib + radiation therapy | I | NCT03945721 | |
| Breast inflammatory carcinoma | Olaparib + radiation therapy | II | NCT03598257 | |
| Malignant glioma without H3 K27M or BRAFV600 mutations | Veliparib + radiation therapy + temozolomide | II | NCT03581292 | |
| Head and neck neoplasms | Olaparib + radiotherapy | I | NCT02229656 | |
| Malignant gliomas | Temozolomide (TMZ) + radiotherapy | I/II | NCT03212742 | |
| ATM | ||||
| Brain cancer | AZD1390 + radiation therapy | I | NCT03423628 | |
| Advanced cancer | XRD‐0394 + palliative radiotherapy | I | NCT05002140 | |
| WEE1 | ||||
| Esophageal adenocarcinoma | Adavosertib + radiation therapy | I | NCT04460937 | |
| Cervical carcinoma | Adavosertib + cisplatin/radiation therapy | I | NCT03345784 | |
| DNA‐PK | ||||
| Rectal cancer | Peposertib + capecitabine/radiotherapy | I/II | NCT03770689 | |
| Solid tumors | M3814 + radiotherapy | I | NCT03724890 | |
| Advanced solid tumors | M3814 + fractionated RT/cisplatin | I | NCT02516813 | |
| Glioblastoma, gliosarcoma | Nedisertib + radiation therapy/ temozolomide | I | NCT04555577 | |
| Advanced solid tumor | XRD‐0394 + palliative radiotherapy | I | NCT05002140 | |
| Other target therapy | ||||
| PARP | ||||
| BRCA1/2 gene mutated tumors | Niraparib + copanlisib (PI3Ki) | I | NCT03586661 | |
| HER2 positive breast carcinoma | Niraparib + trastuzumab | I/II | NCT03368729 | |
| Ovarian cancer | Olaparib + cediranib (VEGFR inhibitor) | N/A | NCT02681237 | |
| Ovarian cancer patients | Niraparib + bevacizumab | II | NCT04734665 | |
| Advanced solid tumors | Olaparib + CYH33 (PI3Kα inhibitor) | II | NCT04586335 | |
| Breast cancer | Talazoparib + sacituzumab goviteca | I/II | NCT04039230 | |
| Advanced breast carcinoma | Olaparib + cediranib(VEGFRi) | II | NCT04090567 | |
| Metastatic breast cancer | Talazoparib + belinostat (HDACi) | I | NCT04703920 | |
| Metastatic malignant solid neoplasm | Olaparib + onalespib (Hsp90 inhibitor) | I | NCT02898207 | |
| Ovarian cancer | Niraparib + bevacizumab | I/II | NCT02354131 | |
| High‐grade serous ovarian cancer | Olaparib + paclitaxel | II | NCT04261465 | |
| Ovarian cancer | Olaparib + anlotinib (VEGFRi) | II | NCT04566952 | |
| Breast cancer metastatic | Olaparib + vorinostat (HDACi) | I | NCT03742245 | |
| Endometrial and ovarian cancer | Olaparib + AZD5363 (AKTi) | I/II | NCT02208375 | |
| Metastatic prostate carcinoma, malignant neoplasm in the bone | Olaparib + cediranib (AZD‐2171) (VEGFRi) | II | NCT02893917 | |
| EGFR‐mutated advanced lung cancer | Niraparib + osimertinib (EGFRi) | I | NCT03891615 | |
| Ovarian cancer | Olaparib + cediranib | III | NCT03278717 | |
| Advanced malignant solid neoplasm | Talazoparib tosylate + axitinib/ crizotinib (VEGFRi) | I | NCT04693468 | |
| Endometrial serous adenocarcinoma | Olaparib + DS‐8201a (HER2i) | I | NCT04585958 | |
| Ovarian cancer with no germline BRCA mutation | Olaparib + alpelisib (PIK3i) | III | NCT04729387 | |
| Pancreatic cancer | Olaparib + cobimetinib (MEK/ERK inhibition) | I | NCT04005690 | |
| Recurrent ovarian, primary peritoneal, or fallopian tube cancer | Olaparib + cediranib maleate | II | NCT02345265 | |
| Recurrent ovarian, fallopian tube, or peritoneal cancer | Olaparib + cediranib maleate | I/II | NCT01116648 | |
| Gastric or gastroesophageal junction cancer | Olaparib + ramucirumab (VEGFRi) | I/II | NCT03008278 | |
| Metastatic NSCLC | Olaparib + cediranib | I | NCT02498613 | |
| Ovarian, fallopian tube, or primary peritoneal cancer | Olaparib + cediranib maleate | II/II | NCT02502266 | |
| ATR | ||||
| Chronic lymphocytic leukemia | AZD6738 + acalabrutinib (BTK inhibitor) | I/I | NCT03328273 | |
| Other treatments | ||||
| PARP | ||||
| Neuroendocrine tumors | Talazoparib + 177Lu‐DOTA‐octreotate PRRT | I | NCT05053854 | |
| Prostate cancer with ATM/BRCA1/2 gene mutation | Niraparib + radical prostatectomy | II | NCT04030559 | |
| Prostate cancer | Olaparib + radium Ra223 dichloride | I | NCT03317392 | |
| Neuroendocrine tumors, thymoma, mesothelioma | Olaparib + 177Lu‐DOTA‐TATE | I | NCT04375267 | |
| Prostate carcinoma | Talazoparib + androgen deprivation therapy | II | NCT04734730 | |
| Metastatic castration‐resistant prostate cancer | Rucaparib + Enzalutamide/zbiraterone | I | NCT04179396 | |
| Prostate cancer | Talazoparib + enzalutamide | III | NCT04821622 | |
| ATR | ||||
| SCLC, neuroendocrine cancers | Berzosertib + lurbinectedin | I/II | NCT04802174 | |
*
Data from https://clinicaltrials.gov.