Platinum-Resistant/Refractory (Pt-R/Rf): Treatment given for recurrence occurring less than 6 months after last platinum-based treatment or for progression during last platinum-based treatment
Platinum-Resistant/Refractory (Pt-R/Rf): Treatment given for recurrence occurring less than 6 months after last platinum-based treatment or for progression during last platinum-based treatment
For more detailed information, please click on the clinical trial ID number.
| Drug Class | Trial ID # | Phase | Drugs | Clinical Trial Title | Key Conclusion and Results |
|---|---|---|---|---|---|
| Standard of Care Chemotherapy | |||||
| Chemotherapy | NCT00023907; NCT00191607; Study 30-49; ITSG | II/III | Gemcitabine, Liposomal doxorubicin, Paclitaxel, Topotecan | Compilation of multiple single drug chemotherapy trials for platinum-resistant recurrence | Similar response rates for single-agent gemcitabine, liposomal doxorubicin, topotecan or paclitaxel ORR: median 8% (6.1-20.9%) v. 9/2017 |
| Standard of Care Targeted Drugs | |||||
| DNA Damage Repair Pathway Inhibitors:PARP | NCT01078662 | II | Olaparib | A Phase II, Open Label, Non Randomised, Non Comparative, Multicentre Study to Assess the Efficacy and Safety of Olaparib Given Orally Twice Daily in Patients With Advanced Cancers Who Have a Confirmed Genetic BRCA 1 and/or BRCA2 Mutation (Study 42) | Olaparib shows promising responses in heavily pretreated gBRCA MUT patients ORR: 30% v. 9/2018 |
| DNA Damage Repair Pathway Inhibitors:PARP | Rucaparib FDA Approval Data | II | Rucaparib | Treatment of BRCA-mutated Ovarian Cancer After 2 or More Chemotherapies | Rucaparib shows promising responses in BRCA MUT patients ORR: 25% v. 9/2018 |
| Angiogenesis Inhibitors: VEGF | NCT00976911 | III | Bevacizumab, Liposomal doxorubicin, Paclitaxel, Topotecan | AURELIA: A Multi-center, Open-label, Randomised, Two-arm Phase III Trial of the Effect on Progression Free Survival of Bevacizumab Plus Chemotherapy Versus Chemotherapy Alone in Patients With Platinum-resistant, Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer | Improved ORR and PFS with addition of bevacizumab to liposomal doxorubicin, paclitaxel or topotecan (most evident with paclitaxel), but no OS benefit Pac/PLD/Top+Bev vs Pac/PLD/Top: ORR: 28.2 vs 12.5%* v. 1/2017 |
| Drugs in NCCN Guidelines | |||||
| Chemotherapy | NCT00087087 | II | Pemetrexed | A Phase II Evaluation of Pemetrexed (Alimta, LY231514l, IND # 40061) in the Treatment of Recurrent or Persistent Platinum Resistant Ovarian or Primary Peritoneal Carcinoma | Pemetrexed has favorable antitumor activity with mild and non-cumulative toxicity ORR: 21.4% v. 5/2018 |
| Angiogenesis Inhibitors: VEGF | NCT00097019 | II | Bevacizumab | A Multicenter, Single-Arm, Phase II Trial of Bevacizumab in Subjects With Platinum-Resistant Epithelial Carcinoma of the Ovary or Primary Peritoneal Carcinoma for Whom Subsequent Doxil or Topotecan Therapy Has Failed | Bevacizumab single-agent activity in platinum-resistant patients, but risk of GI-related adverse events ORR: 15.9% v. 7/2017 |
| Angiogenesis Inhibitors: VEGFR/PDGFR | NCT01644825 | II | Paclitaxel, Pazopanib | MITO-11: A Randomized Multicentre Phase II Trial With Pazopanib and Weekly Paclitaxel vs Weekly Paclitaxel in Platinum Resistant or Refractory Ovarian Cancer | Improved ORR and PFS with combination of pazopanib+paclitaxel Pac+Paz vs Pac: ORR: 56 vs 25%* v. 1/2017 |
| Drugs in Clinical Development | |||||
| DNA Damage Repair Pathway Inhibitors:PARP | NCT01540565 | II | Veliparib | A Phase II Evaluation of the Poly (ADP-Ribose) Polymerase (PARP)-1 and -2 Inhibitor Veliparib (ABT-888) (NSC#737664) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Who Carry a Germline BRCA1 or BRCA2 Mutation | Veliparib shows encouraging activity in gBRCA MUT cancer ORR: 20% v. 1/2017 |
| DNA Damage Repair Pathway Inhibitors:PARP | NCT02354586 | II | Niraparib | A Phase 2, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of Niraparib in Patients With Advanced, Relapsed, High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Have Received Three or Four Previous Chemotherapy Regimens (QUADRA) | Niraparib shows promising activity in late-line treatment setting BRCA MUT: v. 11/2018 |
| DNA Damage Repair Pathway Inhibitors:PARP | NCT02657889 | I/II | Niraparib, Pembrolizumab | Phase 1/2 Clinical Study of Niraparib in Combination With Pembrolizumab (MK-3475) in Patients With Advanced or Metastatic Triple-Negative Breast Cancer and in Patients With Recurrent Ovarian Cancer (TOPACIO) | Promising activity of niraparib + pembrolizumab combination in Pt-R/Pt-Rf patients independent of BRCA status, HRD status and PD-L1 expression BRCA WT: v. 6/2018 |
| Antibody (and other Targeted) Drug Conjugates: FRalpha | NCT01609556 | I | Mirvetuximab Soravtansine | A Phase 1, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of IMGN853 in Adults With Ovarian Cancer and Other FOLR1-Positive Solid Tumors | Mirvetuximab soravtansine shows promising activity in platinum-resistant FRalpha-positive patients who had ≤3 prior therapies ≤3 prior therapies vs >3 prior therapies: ORR: 39 vs 13% v. 8/2018 |
| Antibody (and other Targeted) Drug Conjugates: Mesothelin | NCT02751918 | Ib | Anetumab ravtansine, Liposomal doxorubicin | An Open-label Phase Ib Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Maximum Tolerated Dose of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin 30 mg/m2 Given Every 3 Weeks in Subjects With Mesothelin-expressing Platinum-resistant Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer | Anetumab ravtansine+liposomal doxorubicin combination shows promising activity in platinum-resistant mesothelin-positive patients ORR: 52% v. 6/2018 |
| Angiogenesis Inhibitors: VEGF | NCT02606305 | Ib | Bevacizumab, Mirvetuximab Soravtansine | A Phase 1b/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Mirvetuximab Soravtansine (IMGN853) in Combination With Bevacizumab, Carboplatin, Pegylated Liposomal Doxorubicin, Pembrolizumab, or Bevacizumab+Carboplatin in Adults With Folate Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer | Encouraging activity of bevacizumab+mirvetuximab soravtansine combination in FRalpha-positive patients ORR: 43% v. 8/2018 |
| Angiogenesis Inhibitors: VEGF/DLL4 | NCT03030287 | Ib | Navicixizumab, Paclitaxel | A Phase 1b Study of OMP-305B83 Plus Weekly Paclitaxel in Subjects With Platinum Resistant Ovarian, Primary Peritoneal or Fallopian Tube Cancer | Promising activity of navicixizumab+paclitaxel combination in heavily pretreated patients ORR: 42% |
| Signaling Pathway Inhibitors: PI3K-AKT-mTOR/pan-PI3K | NCT01623349 | I | Buparlisib, Olaparib | Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent Triple Negative Breast Cancer or Recurrent High Grade Serous Ovarian Cancer | Encouraging activity of buparlisib+olaparib, but serious CNS adverse events ORR: 27% v. 5/2017 |
| Signaling Pathway Inhibitors: PI3K-AKT-mTOR/PI3Kalpha | NCT01623349 | I | Alpelisib, Olaparib | Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent Triple Negative Breast Cancer or Recurrent High Grade Serous Ovarian Cancer | Encouraging activity of alpelisib+olaparib combination independent of gBRCA status ORR: 36% v. 5/2017 |
| Signaling Pathway Inhibitors: JAK-STAT/STAT3 | NCT01325441 | II | Napabucasin, Paclitaxel | A Phase Ib/II Clinical Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies | Promising responses to napabucasin+paclitaxel in heavily pretreated patients ORR: 20% v. 6/2018 |
| Cell Cycle Inhibitors: CHK1/2 | NCT02203513 | II | Prexasertib | A Phase II Single Arm Pilot Study of the Chk1/2 Inhibitor (LY2606368) In BRCA1/2 Mutation Associated Breast or Ovarian Cancer, Triple Negative Breast Cancer, and High Grade Serous Ovarian Cancer | Promising activity in heavily pretreated platinum-resistant gBRCA WT patients, including those with CCNE1 aberrations ORR: 32% v. 6/2018 |
| Cell Cycle Inhibitors: Wee1 | NCT01164995 | II | Adavosertib, Carboplatin | Phase II Pharmacological Study With Wee-1 Inhibitor MK-1775 Combined With Carboplatin in Patients With p53 Mutated Epithelial Ovarian Cancer and Early Relapse (< 3 Months) or Progression During Standard First Line Treatment | Promising activity of adavosertib+carboplatin combination in TP53-mutated primary platinum-resistant and platinum-refractory patients ORR: 43% v. 8/2018 |
| Immunotherapy: Checkpoint Inhibitors/PD-1 | NCT02865811 | II | Liposomal doxorubicin, Pembrolizumab | A Phase II Study of Pembrolizumab Combined With Pegylated Liposomal Doxorubicin (PLD) For Recurrent Platinum Resistant Ovarian, Fallopian Tube Or Peritoneal Cancer | Encouraging anti-tumor activity of pembrolizumab+liposomal doxorubicin combination with acceptable safety profile ORR: 19% v. 4/2018 |
| Immunotherapy: Checkpoint Inhibitors/PD-1 | UMIN000005714 | II | Nivolumab | A Phase II trial of immunotherapy with an anti-PD-1 antibody in advanced / relapsed, Platinum - resistant Ovarian Cancer | Encouraging anti-tumor activity of single-agent nivolumab with acceptable safety profile ORR: 15% v.1/2017 |
| Immunotherapy: Checkpoint Inhibitors/PD-1 | NCT02606305 | Ib | Mirvetuximab Soravtansine, Pembrolizumab | A Phase 1b/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Mirvetuximab Soravtansine (IMGN853) in Combination With Bevacizumab, Carboplatin, Pegylated Liposomal Doxorubicin, Pembrolizumab, or Bevacizumab+Carboplatin in Adults With Folate Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer | Encouraging activity of pembrolizumab + mirvetuximab soravtansine combination in FRalpha-positive patients ORR: 30% v. 11/2018 |
| Immunotherapy: Checkpoint Inhibitors/PD-1 | NCT01772004 | I | Avelumab | A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of Avelumab (MSB0010718C) in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications | Avelumab shows encouraging activity with acceptable safety profile ORR: 9.7% v. 6/2018 |
| Immunotherapy: Checkpoint Inhibitors/PD-1 | NCT02054806 | I | Pembrolizumab | Phase IB Study of MK-3475 in Subjects With Select Advanced Solid Tumors | Pembrolizumab shows encouraging anti-tumor activity with acceptable safety profile ORR:12% v. 11/2017 |
| Immunotherapy: Checkpoint Inhibitors/PD-L1 | NCT02580058 | III | Avelumab, Liposomal doxorubicin | A Phase 3, Multicenter, Randomized, Open-Label Study Of Avelumab (MSB0010718C) Alone Or In Combination With Pegylated Liposomal Doxorubicin Versus Pegylated Liposomal Doxorubicin Alone In Patients With Platinum-Resistant/Refractory Ovarian Cancer | Avelumab alone or in combination with liposomal doxorubicin does not significantly improve ORR, PFS or OS versus PLD alone PLD vs Ave vs Ave+PLD: ORR: 4.2 vs 3.7 vs 13.3% v. 11/2018 |
| Immunotherapy: Checkpoint Inhibitors/PD-L1 | NCT02431559 | II | Durvalumab, Liposomal doxorubicin | A Phase 1/2 Study of Chemo-immunotherapy With Toll-like Receptor 8 Agonist Motolimod (VTX-2337) and Anti-PD-L1 Antibody MEDI4736 in Subjects With Recurrent, Platinum-Resistant Ovarian Cancer for Whom Pegylated Liposomal Doxorubicin (PLD) is Indicated | The combination of durvalumab+liposomal doxorubicin has a tolerable safety profile and promising efficacy ORR: 15% v. 11/2018 |