Table 4.
Investigational combination regimens in patients with advanced ovarian cancer
| Clinical Trial | CT | P | I | A | Treatment | Patient Populationa | Phase | Primary EP |
|---|---|---|---|---|---|---|---|---|
| Chemotherapy-based combinations (CT ± PARPi ± anti-PD-1/PD-L1 antibody ± VEGFRi) | ||||||||
| FIRST/ENGOT-ov44 (NCT03602859) | m | Platinum-based CT + TSR-042 (dostarlimab) followed by niraparib + TSR-042 vs CT followed by niraparib maintenance vs CT |
1st line, stage III–IV OvCa | Randomized, double-blind, phase III | PFS | |||
| KEYLYNK-001/ENGOT-ov43 (NCT03740165) | m | CT (carboplatin/paclitaxel) + pembrolizumab followed by olaparib maintenance or CT (carboplatin/paclitaxel) + pembrolizumab vs CT (carboplatin/paclitaxel) (study arms may include bev) |
1st line, BRCA non-mutated OvCa | Randomized, double-blind, phase III | PFS, OS | |||
| IMagyn050/GOG 3015/ENGOT-ov39 (NCT03038100) | CT (carboplatin/paclitaxel) + atezolizumab + bev followed by maintenance atezolizumab + bev vs CT (carboplatin/paclitaxel) + bev followed by bev |
Stage III–IV OvCa after tumor-reductive surgery | Randomized, double-blind, phase III | PFS, OS | ||||
| DUO-O/ENGOT-ov46 (NCT03737643) |
m | m | CT + durvalumab followed by maintenance durvalumab + olaparib + optional bev | Newly diagnosed OvCa, BRCA-mutated | Randomized, open-label, phase III | PFS | ||
| DUO-O/ENGOT-ov46 (NCT03737643) |
m | CT + durvalumab + bev followed by maintenance durvalumab + olaparib + bev vs CT + durvalumab + bev followed by maintenance durvalumab + bev vs CT + bev followed by maintenance bev |
Newly diagnosed OvCa, non BRCA-mutated | Randomized, double-blind, phase III | PFS | |||
| ATHENA/ENGOT-ov45 (NCT03522246) |
m | m | Platinum-based CT followed by maintenance rucaparib + nivolumab vs rucaparib vs nivolumab vs placebo |
Responders to front-line chemotherapy | Randomized, double-blind, phase III | PFS | ||
| ICON 9 (NCT03278717) | m | m | Platinum-based CT followed by maintenance olaparib + cediranib vs platinum-based CT followed by maintenance olaparib |
Relapsed, platinum-sensitive OvCa (responders ≥4 cycles of CT) | Randomized, open-label, phase III | PFS, OS | ||
| ANITA/ENGOT-ov41/GEICO 69-O (NCT03598270) | m | Platinum-based CT (investigator’s choice) + atezolizumab followed by maintenance niraparib + atezolizumab vs CT (investigator’s choice) followed by maintenance niraparib |
Recurrent OvCa, TFIp >6 mos | Randomized, double-blind, phase III | PFS | |||
| ATALANTE (NCT02891824) | Platinum-based CT + atezolizumab + bev ± maintenance atezolizumab + bev vs platinum-based CT + bev followed by maintenance bev |
Recurrent OvCa, TFIp >6 mos | Randomized, double-blind, phase III | PFS | ||||
| NRG-GY009 (NCT02839707) | Pegylated liposomal doxorubicin (PLD) + atezolizumab or PLD + atezolizumab + bevacizumab vs PLD + bevacizumab |
Platinum-resistant OvCa | Randomized, open-label, phase II–III | PFS, OS | ||||
| PARPi + VEGFRi combinations | ||||||||
| NSGO-AVANOVA2/ENGOT-ov24 (NCT02354131) |
Niraparib + bev vs niraparib | Relapsed, platinum-sensitive OvCa | Randomized, open-label, phase II | PFS | ||||
| NRG-GY004 (NCT02446600) | Olaparib + cediranib or olaparib vs standard platinum-based CT |
Relapsed, platinum-sensitive OvCa | Randomized, open-label, phase III | PFS | ||||
| NRG-GY005/COCOS (NCT02502266) | Cediranib + olaparib vs cediranib vs SOC CT (physician’s choice) | Recurrent, platinum-resistant/refractory OvCA (high-grade for BRCA1/2 non-mutation carriers) | Randomized, open-label, phase III | PFS, OS | ||||
| OCTOVA (NCT03117933) | Olaparib + cediranib vs olaparib vs paclitaxel | Platinum-resistant OvCa | Randomized, open-label, phase II | PFS | ||||
| PARPi + anti-PD-1/PD-L1 antibody combinations | ||||||||
| TOPACIO/KEYNOTE-162 (NCT02657889) | Niraparib + pembrolizumab | Recurrent OvCa | Open-label, phase I–II | ORR | ||||
| Javelin PARP Medley (NCT03330405) | Talazoparib + avelumab | Recurrent, platinum-sensitive including BRCA-mutated OvCa | Open-label, phase Ib-II | ORR | ||||
| NCT02660034 | BGB-290 (pamiparib) + BGB-A317 (tislelizumab) | Recurrent, platinum-sensitive (TFIp >6) mos), high-grade OvCa | Open-label, phase I | ORR | ||||
| ARIES (NCT03824704) | Rucaparib + nivolumab | Relapsed, platinum-sensitive OvCa | Open-label, phase II | ORR | ||||
| NCT02484404 | Olaparib + durvalumab | Recurrent, platinum-resistant OvCa | Open-label, phase II | ORR | ||||
| PARPi + anti-PD-1/PD-L1 antibody + VEGFRi combinations | ||||||||
| NCT02484404 | Durvalumab + olaparib + cediranib, durvalumab + olaparib, and durvalumab + cediranib |
Recurrent, platinum-sensitive or resistant OvCa | Non-randomized, open-label, phase II | ORR | ||||
| MEDIOLA (NCT02734004) | Durvalumab + olaparib + bevacizumab and durvalumab + olaparib |
Relapsed, platinum-sensitive OvCa | Non-randomized, open-label, phase II | ORR | ||||
| NCT02873962 | Nivolumab + rucaparib + bevacizumab, nivolumab + bevacizumab | Relapsed, platinum-sensitive or resistant OvCa | Non-randomized, open-label, phase II | ORR | ||||
| NSGO/AVANOVA-Triplet (NCT03806049) | TSR-042 + niraparib + bevacizumab, niraparib + bevacizumab, and carboplatin + paclitaxel |
Recurrent, platinum-sensitive OvCa | Randomized, open-label, phase III | PFS | ||||
| OPAL (NCT03574779) | TSR-042 + niraparib + bevacizumab | Recurrent, platinum-resistant OvCa | Open-label, phase II | ORR | ||||
| anti-PD-1/PD-L1 antibody + VEGFRi combination | ||||||||
| NCT04068974 | Camrelizumab + apatinib | Recurrent, platinum-resistant OvCa | Open-label, phase II | ORR | ||||
aClinical trials may include patients with other tumor types in addition to patients with advanced ovarian cancer. A: angiogenesis inhibition, bev: bevacizumab, CT: chemotherapy, m: maintenance, EP: endpoint, I: PD-1/PD-L1 immune checkpoint inhibition, ORR: objective response rate, OS: overall survival, OvCa: ovarian cancer, P: PARP inhibition, PARPi: PARP inhibitor, PD-1: programmed death 1 receptor, PD-L1: PD-ligand 1, PFS: progression-free survival, SOC: standard of care, TFIp: platinum treatment-free interval, VEGFRi: vascular endothelial growth factor receptor inhibitor.