Table 4.
Combinations therapy of PARPi with Inhibitors of DDR, CDKs, epigenetics drugs and others in Clinical Trials
| Drugs | Clinical Trial ID | Phase | Treatment | Status | Study Population | Outcomes |
|---|---|---|---|---|---|---|
| NCT02723864 | I | Veliparib + VX-970 | Active, not recruiting | Refractory solid tumors | ||
| NCT04267939 | I | Niraparib + BAY1895344 | Recruiting | Advanced solid tumors and ovarian cancer | ||
| NCT02576444 (OLAPCO) | II | Olaparib + AZD6738 | Active, not recruiting | Tumors harboring HDR gene mutations, including ATM, CHK2, APOBEC, MRE11 complex | ||
| NCT04065269 (ATARI) | II | Olaparib + AZD6738 | Recruiting | Gynecological cancers with ARID1A loss or no loss | ||
| NCT03787680 (TRAP) | II | Olaparib + AZD6738 | Active, not recruiting | Metastatic Castration-Resistant Prostate Cancer | ||
| NCT03878095 | II | Olaparib + AZD6738 | Recruiting | IDH1 and IDH2 mutant tumors | ||
| NCT03462342 (CAPRI) | II | Olaparib + AZD6738 | Recruiting | HGSC | ||
| PARPi-ATRi | NCT03428607 (SUKSES-N2) | II | Olaparib + AZD6738 | Completed | SCLC | |
| NCT03682289 | II | Olaparib + AZD6738 | Recruiting | Clear cell renal cell cancer; metastatic renal cell cancer; metastatic urothelial cancer; metastatic pancreatic cancer; locally advanced pancreatic cancer | ||
| NCT04417062 | II | Olaparib + Ceralasetib | Recruiting | Recurrent or refractory sarcoma | ||
| NCT04090567 | II | Olaparib + Ceralasetib/AZD6738 | Recruiting | BRCA mutant advanced breast cancer | ||
| NCT04655183 | II | Niraparib + M4344/VX-803 | Withdrawal | Advanced solid tumors | ||
| NCT04239014 (DUETTE) | II | Olaparib + Ceralasetib | Withdrawal | Platinum sensitive relapsed epithelial ovarian cancer | ||
| NCT03330847 (VIOLETTE) | II | Olaparib + AZD6738 | Active, not recruiting | Metastatic triple negative breast cancer stratified by alterations of HRR-related genes | ||
| PARPi-CHK1i | NCT03057145 | I | Olaparib + Prexasertib | Completed | Advanced solid tumors | |
| PARPI-ATMi | No clinical trials | |||||
| NCT03579316 (EFFORT) | II | Olaparib + AZD1775/Adavosertib | Recruiting | Recurrent fallopian tube, ovarian and primary peritoneal cancers | Adavosertib: ORR = 23%; median PFS = 5.5 mo; median duration of response = 5.5 mo; Adavosertib + Olaparib: ORR = 29%; median PFS = 6.8 mo; median duration of response = 6.4 mo | |
| NCT04197713 (STAR study) | I | Olaparib + AZD1775 | Recruiting | Advanced solid tumors with selected mutations and PARP Resistance | ||
| PARPi-WEE1i | NCT02576444 (OLAPCO) | II | Olaparib + AZD1775 | Active, not recruiting | Tumors harboring either TP53 or KRAS mutations or mutations in KRAS and TP53 | |
| NCT02511795 | Ib | Olaparib + AZD1775 | Completed | Refractory solid tumors | ORR for the total population, cohort 4.2 (A: 175 mg BID + O: 200 mg BID) and cohort 7.4 (A: 200 mg QD + O: 200 mg BID) was 11.1%, 30.8% and 0%, respectively, and the DCR was 55.7%, 76.9% and 53.8%. | |
| NCT03330847 (VIOLETTE) | II | Olaparib + AZD1775 | Active, not recruiting | Metastatic triple negative breast cancer stratified by alterations of HRR-related genes | ||
| PARPi-MYT1i | No clinical trials | |||||
| PARPi-POLqi | NCT04991480 | I/II | Talazoparib + ART4215 | Recruiting | Metastatic breast cancer | |
| PARPi- HSP90i | NCT02627430 | I | Talazoparib + AT13387 | Withdrawal | Metastatic solid tumor or recurrent ovarian, fallopian tube, primary peritoneal, or triple negative breast cancer | |
| NCT02898207 | I | Olaparib + AT13387/Onalespib | Active, not recruiting | Metastatic solid tumor or recurrent ovarian, fallopian tube, primary peritoneal, or triple negative breast cancer | ||
| PARPi-AKTi | NCT02576444 (OLAPCO) | II | Olaparib + AZD5363/capivasertib | Active, not recruiting | Tumors harboring PTEN, PIK3CA, AKT, or ARID1A mutations or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway | |
| NCT02208375 | I/II | Olaparib + AZD5363/capivasertib | Active, not recruiting | BRCA mutant recurrent endometrial and ovarian cancer | ||
| PARPi-CDKi | NCT01434316 | I | Veliparib/ABT888 + Dinaciclib | Recruiting | Advanced solid tumors | |
| NCT04355858 (MULAN) | II | SHR3162 + SHR6390 (CDK4/6i) | Recruiting | HR+/HER2- endocrine-resistant advanced breast cancer | ||
| PARPi-mTOR1/2i | NCT02208375 | Ib/II | Olaparib + AZD2014/vistusertib | Active, not recruiting | BRCA mutant recurrent endometrial and ovarian cancer | Mean response rate = 19%; median duration = 14 mos.; clinical benefit rate = 34% |
| PARPi-MEK/ERKi | NCT04005690 | I | Olaparib + Cobimetinib | Recruiting | Pancreatic cancer | |
| PARPi-MEKi-PD1 | NCT03182673 | I | SHR3162 + SHR7390 + SHR1210 | N.A. | Advanced solid tumors | |
| NCT04586335 | I | Olaparib + CYH33 | Recruiting | Ovarian, breast, prostate and endometrial cancers | ||
| PARPi-PI3Ki | NCT01623349 | I | Olaparib + BKM120 or BYL719 | Completed | Recurrent TNBC or HGSOC | 36% patients achieved a partial response and 50% patients had stable disease. |
| NCT03586661 | I | Niraparib + Copanlisib | Recruiting | Recurrent endometrial, ovarian, primary peritoneal, or fallopian tube cancer | ||
| PARPi-VEGFi | NCT01116648 | II | Olaparib + cediranib/AZD2171 | Completed | Non-BRCA mutant recurrent platinum resistant ovarian cancer (N = 90) | Median PFS was 17.7 months for women with cediranib plus olaparib combination treatment compared with 9.0 months for those with olaparib monotherapy. |
| NCT02889900 (CONCERTO) | Iib | Olaparib + cediranib/AZD2171 | Completed | Non-BRCA mutant recurrent platinum resistant ovarian cancer (N = 62) | Objective response rate = 15.3%; median PFS = 5.1 months; median duration of response = 8.3 months; median OS = 13.2 months. | |
| NCT03742245 | I/Ib | Olaparib + Vorinostat/SAHA | Recruiting | Relapsed/refractory and/or metastatic breast cancer | ||
| NCT04703920 | I | Talazoparib + Belinostat | Recruiting | Metastatic breast cancer, metastatic castration resistant prostate cancer, and metastatic ovarian cancer | ||
| PARPi- epigenetic drugs | NCT03259503 | I | Olaparib + multiple chemo including Vorinostat | Recruiting | Relapsed or refractory lymphomas undergoing stem cell transplant | |
| NCT02878785 | I/II | Talazoparib + Decitabine/Dacogen (DAC) | Active, not recruiting | Untreated AML and Relapsed/refractory AML | ||
| NCT04355858 (MULAN) | II | SHR3162 + SHR2554 (EZH2i) | Recruiting | HR+/HER2- endocrine-resistant advanced breast cancer |
HGSC: high-grade serous carcinoma; SCLC, small cell lung cancer; TNBC, triple-negative breast cancer; AML, acute myeloid leukemia; HRR, homologous recombination repair; DCR, disease control rate; ORR, objective response rate; PFS, progression-free survival; BID/b.i.d., twice a day; QD/q.d., every day; mo, month