Table 4. Olaparib as combination therapy.
MTD: maximum tolerated dose; BRCA: breast cancer-associated; ATM: ataxia-telangiectasia mutated; HRD: homologous recombination deficiency; DDR: DNA damage repair
| Clinical trial | Phase | Study objective | Germline mutations | Somatic mutations | Outcomes |
| Olaparib with chemotherapy and targeted therapy | |||||
| NCT00515866 [36] | Phase I | Evaluate the safety and MTD of olaparib with gemcitabine versus gemcitabine alone in patients with locally advanced/metastatic pancreatic cancer | Unselected for mutations | Out of 66 patients treated, olaparib 100 mg twice daily with gemcitabine 600 mg/m2 was the most tolerable combination. | |
| NCT01296763 [37] | phase I | Dose escalation trial evaluating olaparib in combination with irinotecan, cisplatin, and mitomycin C in patients with advanced pancreatic cancer | Known BRCA-mutated or Jewish ancestry patients and those with familial and sporadic pancreatic cancer were included | Early closure due to toxicity | |
| NCT03682289 [38] | phase II | Studying the efficacy of ATR kinase inhibitor AZD6738 alone versus combination with olaparib in patients with advanced renal cell, urothelial and pancreatic cancers | N/A | BAF250a-positive received AZD6738 with olaparib and BAF250a-negative or ATM-mutant received AZD6738 only | Currently recruiting |
| NCT02498613 [39] | Phase II | Study evaluating cediranib maleate combined with olaparib in advanced breast, non-small-cell and small-cell lung cancer, and pancreatic cancer patients | Identification of DNA repair genes in tumors using the BROCA panel with a plan to correlate tumor regression with mutations status | Currently recruiting | |
| NCT03205176 [40] | Phase I | Study evaluating MTD and preliminary antitumor activity of AZD5153 in relapsed/refractory malignant solid tumor, including lymphoma patients as a single agent or in combination with olaparib. | Patients are included regardless of BRCA status. Planned to collect BRCA and HRD gene mutational status | Currently recruiting | |
| NCT04005690 [41] | Phase II window of opportunity trial | Evaluating cobimetinib or olaparib response in patients with resectable pancreatic cancer by comparing pretreatment biopsy samples with posttreatment resection specimens | N/A | Currently recruiting | |
| Olaparib with immunotherapy | |||||
| NCT03851614 (DAPPER) [42] | Phase II | Evaluating changes in genomic and immune biomarkers in tumor, peripheral blood, and stool; changes in radiomic profiles, with the combination of durvalumab with olaparib or cediranib | Patients with germline or somatic DDR genes will be evaluated retrospectively but is not an eligibility criteria | Currently recruiting | |