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
Objective Response Rate (%)
Percentage of patients whose tumors shrink or go away after treatment
Progression Free Survival (months)
Median length of time before the cancer comes back or gets worse
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 | NCT00191607 | III | Gemcitabine, Liposomal doxorubicin | A Randomized Phase III Trial of Gemzar Versus Doxil With Crossover Treatment Option for Patients With Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer Undergoing Second or Third-Line Chemotherapy | Comparable efficacy for liposomal doxorubicin and gemcitabine with different toxicity profiles PLD vs Gem: ORR: 8.3 vs 6.1% pub 2007 |
| Chemotherapy | Study 30-49; Trial 4 | III | Liposomal doxorubicin, Topotecan Prescribing Information | Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan | Liposomal doxorubicin and topotecan have similar efficacy, but very different toxicity profiles PLD vs Top: ORR: 12.3 vs 6.5% pub 2001 |
| Chemotherapy | NCT00023907 | II | Paclitaxel | A Phase II Evaluation of Weekly Paclitaxel in the Treatment of Recurrent or Persistent Platinum and Paclitaxel-Resistant Ovarian or Primary Peritoneal Cancer | Weekly paclitaxel shows promising activity in Pt-R and Pt-Rf patients ORR: 20.9% pub 2006 |
| Standard of Care Targeted Drugs | |||||
| Angiogenesis Inhibitors: VEGF | NCT00976911; AURELIA | III | Bevacizumab, Liposomal doxorubicin, Paclitaxel, Topotecan Prescribing Information | 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%* pub 2014; 2015 |
| DNA Damage Repair Pathway Inhibitors: PARP | NCT01078662; Study 42 | II | Olaparib Prescribing Information | 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 Pt-R gBRCA MUT patients ORR: 30% pub 2016 |
| DNA Damage Repair Pathway Inhibitors: PARP | NCT02354586; QUADRA | II | Niraparib Prescribing Information | 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: pub 2019 |
| DNA Damage Repair Pathway Inhibitors: PARP | Rucaparib FDA Approval Data | II | Rucaparib Prescribing Information | Treatment of BRCA-mutated Ovarian Cancer After 2 or More Chemotherapies | Rucaparib shows promising responses in BRCA MUT patients ORR: 25% pub 2018 |
| Drugs in NCCN Guidelines | |||||
| Chemotherapy | NCT00002478 | II | Etoposide | Phase II Study of Prolonged Oral VP-16 for Advanced Ovarian Epithelial and Cervical Cancer | Prolonged etoposide regimen shows activity, but has hematologic toxicity ORR: 26.8% pub 1998 |
| Chemotherapy | NCT00004037 | II | Docetaxel | Evaluation of Docetaxel in Recurrent, Platinum Resistant, Refractory and Paclitaxel Refractory Ovarian Cancer and Primary Peritoneal Carcinoma | Docetaxel shows activity, but with significant hematologic toxicity ORR: 22.4% pub 2003 |
| 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% pub 2009 |
| DNA Damage Repair Pathway Inhibitors: PARP | NCT02354586; QUADRA | 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 some activity in late-line treatment setting HRD+ (incl. BRCA MUT): HRD+ (excl. BRCA MUT): pub 2019 |
| 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 has single-agent activity, but risk of GI-related adverse events ORR: 15.9% pub 2007 |
| Angiogenesis Inhibitors: VEGF | Retrospective Study: Cyc + Bev | II | Bevacizumab, Cyclophosphamide | The combination of intravenous bevacizumab and metronomic oral cyclophosphamide is an effective regimen for platinum-resistant recurrent ovarian cancer | Cyclophosphamide+bevacizumab is an effective, well-tolerated combination in heavily pretreated patients ORR: 42.4% pub 2013 |
| Drugs in Clinical Development | |||||
| Chemotherapy | NCT00025155 | II | Ixabepilone | A Phase II Evaluation of Epothilone-B BMS 247550 (NSC # 710428) in the Treatment of Recurrent or Persistent Platinum and Paclitaxel Refractory Ovarian or Primary Peritoneal Cancer | Weekly ixabepilone has antitumor activity and acceptable toxicity ORR: 14.3% pub 2010 |
| Chemotherapy | Rose (2003) CisPt+Gem | II | Cisplatin, Gemcitabine | Phase II study of cisplatin plus gemcitabine in platinum-resistant and platinum-refractory ovarian cancer | Cisplatin+gemcitabine is active in Pt-R and Pt-Rf patients ORR: 42.9% pub 2003 |
| DNA Damage Repair Pathway Inhibitors: PARP | NCT03314740; BAROCCO | II | Cediranib, Olaparib | The BAROCCO Study (Best Approach in Recurrent-Ovarian-Cancer-with Cediranib-Olaparib): an Italian Multicenter Randomized Phase II Study of Weekly Paclitaxel vs. Cediranib-Olaparib With Continuous Schedule vs. Cediranib-Olaparib With Intermittent Schedule in Patients With Platinum Resistant High Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. | Olaparib+cediranib (continuous dosing) shows a promising trend towards improved PFS in comparison with weekly paclitaxel, in particular in BRCA WT patients Ola+Ced (continuous) vs Ola+Ced (intermittent) vs Pac: gBRCA WT: abs Oct 2019 |
| DNA Damage Repair Pathway Inhibitors: PARP | NCT02657889; TOPACIO | 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 independent of BRCA status, HRD status and PD-L1 expression ORR: 18% pub 2019 |
| DNA Damage Repair Pathway Inhibitors: PARP | NCT02660034 | I/Ib | Pamiparib, Tislelizumab | A Phase 1/1b, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activity of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Combination With the PARP Inhibitor BGB-290 in Subjects With Advanced Solid Tumors | Pamiparib+tislelizumab is well tolerated and associated with antitumor responses in both BRCA WT and BRCA MUT ovarian cancer 18 evaluable Pt-R: pub 2019 |
| DNA Damage Repair Pathway Inhibitors: ATR | NCT02595892 | II | Berzosertib, Gemcitabine | Phase 2 Study of M6620 (VX-970) in Combination With Gemcitabine Versus Gemcitabine Alone in Subjects With Platinum-Resistant Recurrent Ovarian or Primary Peritoneal Fallopian Tube Cancer | Addition of berzosertib to gemcitabine increased PFS without additional toxicity Ber+Gem vs Gem: PFS: 5.7 vs 3.7 months* abs Oct 2019 |
| Antibody Drug Conjugates: FRalpha | NCT02631876; FORWARD I | III | Liposomal doxorubicin, Mirvetuximab Soravtansine, Paclitaxel, Topotecan | FORWARD I: A Randomized, Open Label Phase 3 Study to Evaluate the Safety and Efficacy of Mirvetuximab Soravtansine (IMGN853) Versus Investigator's Choice of Chemotherapy in Women With Folate Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer | Mirvetuximab soravtansine has favorable tolerability and benefit-risk profile compared to chemotherapy in FRalpha high patients Mir vs TPC (PLD, Pac, Top): FRalpha high (10X scoring method): ORR: 24 vs 10%* FRalpha high (PS2+ scoring method): ORR: 26 vs 6%* abs Oct 2019 |
| Antibody Drug Conjugates: FRalpha | NCT02606305; FORWARD II-2 | Ib/II | 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 | The combination of mirvetuximab soravtansine with bevacizumab demonstrates an encouraging ORR in platinum resistant patients with high FRalpha expression ORR: 59% abs May 2020 and presentation |
| Antibody Drug Conjugates: FRalpha | NCT02996825 | I | Gemcitabine, Mirvetuximab Soravtansine | A Phase I Dose-Escalation Safety and Tolerability Study of MirvetuximabSoravtansine (IMGN853) and Gemcitabine in Patients With FRa-positive Recurrent Ovarian, Primary Peritoneal, Fallopian Tube, Endometrial Cancer, or Triple Negative Breast Cancer (TNBC) | Mirvetuximab soravtansine+gemcitabine can be combined at clinically relevant doses with promising efficacy, particularly in FRalpha med/high tumors ORR: 42.9% (n=14) abs May 2019 and poster |
| Antibody Drug Conjugates: Axl | NCT02988817 | I/II | Enapotamab Vedotin | First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of Axl-specific Antibody-drug Conjugate (Enapotamab Vedotin, HuMax®-AXL-ADC) in Patients With Solid Tumors | Enapotamab Vedotin has a manageable safety profile and encouraging anti-tumor activity in heavily pretreated ovarian cancer patients ORR: 13% (n=15) abs Jun 2019 |
| Antibody Drug Conjugates: NaPi2b | NCT03319628 | Ib | XMT-1536 | A Phase 1b, First-in-Human, Dose Escalation and Expansion Study of XMT-1536 In Patients With Solid Tumors Likely to Express NaPi2b | XMT-1536 is well tolerated and shows promising signs of anti-tumor activity in Pt-R ovarian cancer ORR: 35% abs May 2019, abs May 2020 and presentation |
| Angiogenesis Inhibitors: VEGF | NCT02873962 | II | Bevacizumab, Nivolumab | A Phase II Study With a Safety lead-in of Nivolumab in Combination With Bevacizumab or in Combination With Bevacizumab and Rucaparib for the Treatment of Relapsed Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer | Bevacizumab+nivolumab shows activity in Pt-R patients, independent of PD-L1 expression ORR: 16.7% pub 2019 |
| 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 in heavily pretreated patients ORR: 43.2% abs Mar 2020 |
| Angiogenesis Inhibitors: VEGFR | NCT02788708 | I | Lenvatinib, Paclitaxel | Phase I Evaluation of Lenvatinib and Weekly Paclitaxel in Patients With Recurrent Endometrial, Ovarian, Fallopian Tube, or Primary Peritoneal Cancer | Lenvatinib+weekly paclitaxel shows promising response rates ORR: 71% abs Mar 2019 |
| Angiogenesis Inhibitors: Multi-targeted RTK | NCT03666143 | I | Sitravatinib, Tislelizumab | A Phase 1b Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Sitravatinib in Combination With Tislelizumab in Patients With Advanced Solid Tumors | Combination treatment with sitravatinib and tislelizumab is manageable and shows promising anti-tumor activity ORR: 23.5% abs Dec 2019 |
| 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 High Grade Serous Ovarian Cancer | Encouraging activity of alpelisib+olaparib combination, also in gBRCA WT patients 28 evaluable ovarian Pt-R/Pt-Rf: 17 evaluable gBRCA WT: pub 2019 |
| Signaling Pathway Inhibitors: PI3K-AKT-mTOR/mTOR | NCT01010126 | II | Bevacizumab, Temsirolimus | A Phase 2 Trial of Temsirolimus and Bevacizumab in Patients With Endometrial, Ovarian, Hepatocellular Carcinoma, Carcinoid or Islet Cell Cancer | Temsirolimus+bevacizumab has activity in Pt-R ovarian cancer but with substantial toxicity ORR: 32.1% abs Jun 2013 and poster |
| Immunotherapy: Checkpoint Inhibitors/PD-1 | NCT02440425 | II | Paclitaxel, Pembrolizumab | Phase 2 Trial of Dose Dense (Weekly) Paclitaxel With Pembrolizumab (MK-3475) in Platinum Resistant Recurrent Ovarian Cancer | Pembrolizumab+paclitaxel shows improved ORR and PFS compared to single-agent paclitaxel ORR: 51.4% Press release Feb 2020 |
| Immunotherapy: Checkpoint Inhibitors/PD-1 | NCT02608684 | II | Cisplatin, Gemcitabine, Pembrolizumab | A Phase II Study of Pembrolizumab With Cisplatin and Gemcitabine Treatment in Patients With Recurrent Platinum-resistant Ovarian Cancer | Adding pembrolizumab to cisplatin+gemcitabine and continuing as single-agent maintenance treatment results in promising response rates ORR: 57% (n=14) abs Mar 2019 |
| 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 with acceptable safety profile ORR: 19% abs Mar 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% pub 2015 |
| Immunotherapy: Checkpoint Inhibitors/PD-1 | NCT03029598 | I/II | Carboplatin, Pembrolizumab | Anti-PD-1 Therapy in Combination With Platinum Chemotherapy for Platinum Resistant Ovarian, Fallopian Tube, and Primary Peritoneal Cancer | Promising activity of pembrolizumab with low dose carboplatin in heavily pretreated patients ORR: 13% abs Jun 2019 |
| Immunotherapy: Checkpoint Inhibitors/PD-1 | NCT02054806; KEYNOTE-028 | I | Pembrolizumab | Phase IB Study of Pembrolizumab (MK-3475) in Subjects With Select Advanced Solid Tumors | Pembrolizumab shows encouraging anti-tumor activity with acceptable safety profile ORR:12% pub 2019 |
| Immunotherapy: Checkpoint Inhibitors/PD-L1 | NCT02580058; JAVELIN Ovarian 200 | 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 | No significant improvement in ORR, PFS or OS with avelumab+liposomal doxorubicin compared to avelumab or PLD alone PLD vs Ave vs Ave+PLD: ORR: 4.2 vs 3.7 vs 13.3% abs Nov 2018 |
| Immunotherapy: Checkpoint Inhibitors/PD-L1 | NCT02431559 | II | Durvalumab, Liposomal doxorubicin | Phase 1/2 Study of Chemoimmunotherapy With Toll-like Receptor 8 Agonist Motolimod (VTX-2337) + Anti-PD-L1 Antibody MEDI4736 in Subjects With Recurrent, Platinum-Resistant Ovarian Cancer for Whom Pegylated Liposomal Doxorubicin is Indicated | Durvalumab+liposomal doxorubicin has a tolerable safety profile and promising efficacy ORR: 22.5% abs Mar 2020 |
| Immunotherapy: Checkpoint Inhibitors/PD-L1 | 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 in ovarian cancer ORR: 9.6% pub 2019 |
| Antibody Drug Conjugates: CD166 | NCT03149549 | I/II | CX-2009 | A Phase 1-2, Open-Label, Dose-Finding, Proof of Concept, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CX-2009 in Adults With Metastatic or Locally Advanced Unresectable Solid Tumors (PROCLAIM-CX-2009) | CX-2009 is well tolerated with early evidence of biological activity in Pt-R/Pt-Rf ovarian cancer ORR: 11.1% (2PR) abs May 2020 and poster |
| Immunotherapy: Checkpoint Inhibitors/CD47 | NCT03558139 | Ib | Avelumab, Magrolimab | A Phase 1b Trial of Hu5F9-G4 in Combination With Avelumab in Solid Tumor Patients and Checkpoint Inhibitor Naïve Ovarian Cancer Patients Who Progress Within 6 Months of Prior Platinum Chemotherapy | Magrolimab+avelumab is a novel, well-tolerated combination with a 56% stable disease rate in ovarian cancer patients DCR: 56% (10SD) abs Feb 2020 |
| Oncolytic Viruses | NCT02759588 | Ib/II | Bevacizumab, Docetaxel, Gemcitabine, Liposomal doxorubicin, Olvimulogene Nanivacirepvec (Olvi-Vec), Paclitaxel | Phase 1b & 2 Study With GL-ONC1 Oncolytic Immunotherapy in Patients With Recurrent or Refractory Ovarian Cancer (VIRO-15) | Patients treated with Olvi-Vec-primed immunochemotherapy combined with standard carboplatinum based therapy shows ORR and PFS exceeding historical comparisons and patients’ own last prior therapy. The majority of patients benefit from apparent reversal of platinum resistance Olvi-Vec: Olvi-Vec+CarboPt-based therapy +/- Bev: abs Mar 2020 |
| Oncolytic Viruses | NCT00408590 | I | MV-NIS | Phase I Trial of Intraperitoneal Administration of a) a CEA-Expressing Derivative, and b) a NIS-Expressing Derivative Manufactured From a Genetically Engineered Strain of Measles Virus in Patients With Recurrent Ovarian Cancer | Intraperitoneal administration of MV-NIS is safe with early evidence of antitumor activity and treatment with MV-NIS augments endogenous immunity against tumor antigens DCR: 81.3% pub 2015 |