Results from clinical trials of PARPi in several malignancies
| Clinical trial (EudraCT number)/reference . | Disease . | Therapy . | Potential mechanism . | Results . |
|---|---|---|---|---|
| NCT00753545 L edermann et al, 2014 | Ovarian cancer | Olaparib 400 mg BID vs placebo | Synthetic lethality DNA repair | BRCA+: median PFS significantly longer in the olaparib group OS not significantly different between groups Serious adverse events reported in 25 (18%) patients under olaparib and 11 (9%) under placebo. |
| NCT01891344 Swisher et al, 2017 | Ovarian cancer | Rucaparib 600 mg PO, BID | Homologous recombination deficiency DNA methylation Genomic LOH | BRCA+: PFS longer in high LOH Grade ≥3 treatment-related adverse events: anemia (45 [22%] patients) and elevations in ALT/AST (25 [12%]) |
| NCT01618136 Plummer et al, 2020 | Ovarian cancer, B-cell malignancies, malignant solid tumors, triple-negative breast cancer, advanced melanoma | E7449 50-800 mg QD, PO E7449 plus TMZ QD, PO E7449 plus carboplatin and paclitaxel QD, PO | PARP-DNA trapping Synthetic lethality | Antitumor activity of E7449 in 13 patients, durable in 8. The 2X-121 DRP identified patients achieving PR and durable SD. E7449: good tolerability, promising antitumor activity and significant concentration-dependent PARP inhibition. |
| NCT043260230 Morice et al, 2020 | MDS, AML (review of randomized controlled trials) | Olaparib, rucaparib, niraparib, talazoparib, veliparib | PARPis significantly increased the risk of MDS and AML compared with placebo treatment with no between-study heterogeneity. | |
| NCT03953898 Reference number106 | R/R AML, MDS | Olaparib | Inhibition of cancer cell growth by blocking enzymes needed for cell growth. | No results Still recruiting |
| NCT03974217 Reference number107 | Leukemia | Talazoparib | Synthetic lethality (leukemia cells with a mutation in cohesin may be dependent on PARP activity to survive; when inhibiting PARP with talazoparib the leukemia cells die) | No results Still recruiting |
| NCT00588991 Reference number122 | R/R AML, high-risk MDS, aggressive myeloproliferative disorder | Veliparib Carboplatin Topotecan Hydrochloride | DNA repair cytotoxicity of multiple classes of chemotherapy drugs, including topoisomerase I inhibitors and platinating agents. | No results/not recruiting Veliparib/topotecan/carboplatin combination warrants further investigation |
| NCT04207190 Reference number123 | R/R AML | Gemtuzumab- ozogamicin, talazoparib, talazoparib tosylate | PARP1 trapping Potential ability of talazoparib to enhance levels of DNA damage induced by GO therapy. | Still recruiting |
| NCT02878785 Reference number124 | Untreated AML, R/R AML | Decitabine, talazoparib | SSB repair | Active, not recruiting Suggestion that talazoparib will increase the effects of decitabine in leukemia cells |
| Clinical trial (EudraCT number)/reference . | Disease . | Therapy . | Potential mechanism . | Results . |
|---|---|---|---|---|
| NCT00753545 L edermann et al, 2014 | Ovarian cancer | Olaparib 400 mg BID vs placebo | Synthetic lethality DNA repair | BRCA+: median PFS significantly longer in the olaparib group OS not significantly different between groups Serious adverse events reported in 25 (18%) patients under olaparib and 11 (9%) under placebo. |
| NCT01891344 Swisher et al, 2017 | Ovarian cancer | Rucaparib 600 mg PO, BID | Homologous recombination deficiency DNA methylation Genomic LOH | BRCA+: PFS longer in high LOH Grade ≥3 treatment-related adverse events: anemia (45 [22%] patients) and elevations in ALT/AST (25 [12%]) |
| NCT01618136 Plummer et al, 2020 | Ovarian cancer, B-cell malignancies, malignant solid tumors, triple-negative breast cancer, advanced melanoma | E7449 50-800 mg QD, PO E7449 plus TMZ QD, PO E7449 plus carboplatin and paclitaxel QD, PO | PARP-DNA trapping Synthetic lethality | Antitumor activity of E7449 in 13 patients, durable in 8. The 2X-121 DRP identified patients achieving PR and durable SD. E7449: good tolerability, promising antitumor activity and significant concentration-dependent PARP inhibition. |
| NCT043260230 Morice et al, 2020 | MDS, AML (review of randomized controlled trials) | Olaparib, rucaparib, niraparib, talazoparib, veliparib | PARPis significantly increased the risk of MDS and AML compared with placebo treatment with no between-study heterogeneity. | |
| NCT03953898 Reference number106 | R/R AML, MDS | Olaparib | Inhibition of cancer cell growth by blocking enzymes needed for cell growth. | No results Still recruiting |
| NCT03974217 Reference number107 | Leukemia | Talazoparib | Synthetic lethality (leukemia cells with a mutation in cohesin may be dependent on PARP activity to survive; when inhibiting PARP with talazoparib the leukemia cells die) | No results Still recruiting |
| NCT00588991 Reference number122 | R/R AML, high-risk MDS, aggressive myeloproliferative disorder | Veliparib Carboplatin Topotecan Hydrochloride | DNA repair cytotoxicity of multiple classes of chemotherapy drugs, including topoisomerase I inhibitors and platinating agents. | No results/not recruiting Veliparib/topotecan/carboplatin combination warrants further investigation |
| NCT04207190 Reference number123 | R/R AML | Gemtuzumab- ozogamicin, talazoparib, talazoparib tosylate | PARP1 trapping Potential ability of talazoparib to enhance levels of DNA damage induced by GO therapy. | Still recruiting |
| NCT02878785 Reference number124 | Untreated AML, R/R AML | Decitabine, talazoparib | SSB repair | Active, not recruiting Suggestion that talazoparib will increase the effects of decitabine in leukemia cells |
BID, twice per day; DRP, drug response predictor; EudraCT, European Union Drug Regulating Authorities Clinical Trials Database; GO, gemtuzumab ozogamicin; LOH, loss of heterozygosity; OS, overall survival; PFS, progression-free survival; PO (per os), oral administration; PR, partial response; QD, once a day; SD, stable disease.