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 | Liposomal doxorubicin, Paclitaxel, Topotecan, Bevacizumab 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 |
| Angiogenesis Inhibitors: VEGF | UMIN000017247; JGOG3023 | II | Gemcitabine, Liposomal doxorubicin, Paclitaxel, Topotecan, Bevacizumab | An open-label, randomized, phase II trial evaluating the efficacy and safety of standard of care with or without Bevacizumab in Platinum-resistant ovarian cancer patients previously treated with Bevacizumab for front-line or Platinum-sensitive ovarian cancer: -JGOG3023 trial- | Retreatment with bevacizumab is effective and AEs are manageable for platinum resistant recurrent ovarian cancer previously treated with bevacizumab for front-line or platinum sensitive recurrence Gem/Pac/PLD/Top+Bev vs Gem/Pac/PLD/Top: ORR: 25.0 vs 13.7% pub 2022 |
| 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 |
| Chemotherapy | Retrospective Study: Metronomic Oral Cyclophosphamide (MOC) | II | Cyclophosphamide | Metronomic oral cyclophosphamide (MOC) in the salvage therapy of heavily treated recurrent ovarian cancer patients: a retrospective, multicenter study | Metronomic oral cyclophosphamide may provide a valid alternative for the palliative treatment of heavily pretreated recurrent ovarian cancer ORR: 15% pub 2014 |
| 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: Bevacizumab and Cyclophosphamide | II | Cyclophosphamide, Bevacizumab | 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 |
| Angiogenesis Inhibitors: Multi-targeted RTK | NCT01047891 | II | Sorafenib, Topotecan | A Randomized, Double-blind, Placebo Controlled, Multicenter Phase II Study to Assess the Efficacy and Safety of Sorafenib Added to Standard Treatment With Topotecan in Patients With Platinum-resistant Recurrent Ovarian Cancer | Sorafenib given with topotecan (5-day schedule) and continued as maintenance therapy results in a significant improvement in ORR, PFS and OS ORR: 31 vs 12%* pub 2018 |
| Drugs in Clinical Development | |||||
| 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 | NCT03699449 | II | Cediranib, Olaparib | An uMbrella Study of BIomarker-driven Targeted Therapy In Patients With Platinum-resistant Recurrent OvariaN Cancer(AMBITION) | Olaparib+cediranib shows promising activity in BRCA MUT patients ORR: 50% abs Jun 2021 and poster, pub 2022 |
| DNA Damage Repair Pathway Inhibitors: PARP | NCT02889900; CONCERTO | II | Cediranib, Olaparib | A Single Arm, Open-label, Phase IIb Study to Assess the Efficacy and Safety of the Combination of Cediranib and Olaparib Tablets in Women With Recurrent Platinum Resistant Epithelial Ovarian Cancer, Including Fallopian Tube and/or Primary Peritoneal Cancer Who do Not Carry a Deleterious or Suspected Deleterious Germline BRCA Mutation | Olaparib+cediranib has manageable toxicity and shows evidence of anti-tumor activity in heavily pretreated platinum resistant non-gBRCA MUT patients ORR: 15.6% pub 2022
|
| DNA Damage Repair Pathway Inhibitors: PARP | NCT03574779 | II | Bevacizumab, Dostarlimab, Niraparib | A Phase 1B/2 Multicohort Umbrella Study to Evaluate the Safety and Efficacy of Novel Treatments And/Or Combinations of Treatments in Participants With Ovarian Cancer (OPAL) | Triplet therapy with niraparib, dostarlimab, and bevacizumab is tolerable and demonstrates clinical activity in patients with BRCA WT Pt-R OC without HRR gene mutations ORR: 17.9% w/ prior Bev: ORR: 6% abs Mar 2021 |
| DNA Damage Repair Pathway Inhibitors: PARP | NCT02657889; TOPACIO | I/II | Pembrolizumab, Niraparib | 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 in platinum resistant patients independent of BRCA status, HRD status and PD-L1 expression ORR: 21% pub 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%* pub 2021 |
| Antibody Drug Conjugates: FRalpha | NCT04296890; SORAYA | III | Mirvetuximab soravtansine | SORAYA: A Phase 3, Single Arm Study of Mirvetuximab Soravtansine in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression | Mirvetuximab shows impressive activity and tolerability in FRα-high Pt-R OC ORR: 32.4% abs Mar 2022, abs Jun 2022 and poster |
| Antibody Drug Conjugates: FRalpha | NCT03386942 | I | MORAb-202 | A Phase 1 Study of MORAb-202 in Subjects With Solid Tumors | Anti-tumor activity is seen with both the MORAb-202 0.9 mg/kg and 1.2 mg/kg doses and efficacy is observed irrespective of FRalpha-expression levels 0.9 mg/kg (n=24): ORR: 25% 1.2 mg/kg (n=21) ORR: 52.4% Abs Jun 2022 and posters |
| Antibody Drug Conjugates: FRalpha | NCT03748186 | I | STRO-002 | A Phase 1 Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of STRO-002, an Anti-Folate Receptor Alpha (FolRα) Antibody-Drug Conjugate (ADC), in Patients With Advanced Epithelial Ovarian Cancer (Including Fallopian Tube or Primary Peritoneal Cancers) and Endometrial Cancers | STRO-002 is well tolerated with evidence of anti-tumor activity in heavily pretreated patients. No ocular toxicity signals have been observed. Durable responses and anti-tumor activity have been demonstrated across a broad range of FRα expression levels Results from dose escalation, doses 2.9 mg/kg and above: ORR: 32% abs Jun 2021 and poster |
| Antibody Drug Conjugates: NaPi2b | NCT03319628 | Ib/II | Upifitamab rilsodotin | A Phase 1b/2, First-in-Human, Dose Escalation and Expansion Study of XMT-1536 In Patients With Solid Tumors Likely to Express NaPi2b | UpRi (XMT-1536) is well tolerated and shows promising signs of anti-tumor activity in Pt-R OC; UpRi at the 36mg/m2 dose demonstrates robust clinical activity with a differentiated safety profile Dose group 36 (33-38 mg/m2): NaPi2b High (TPS≥75): press release Nov 2021, abs Mar 2022 |
| Angiogenesis Inhibitors: VEGF | NCT01091259 | II | Bevacizumab, Irinotecan | Phase II Study of Irinotecan in Combination With Bevacizumab for the Treatment of Recurrent Ovarian Cancer | Bevacizumab+irinotecan shows encouraging activity in heavily pre-treated Pt-R patients, including those treated with topotecan and/or avastin ORR: 21% pub 2017 |
| Angiogenesis Inhibitors: VEGF | NCT02873962 | II | Nivolumab, Bevacizumab | 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% pub 2022 |
| Angiogenesis Inhibitors: VEGFR | NCT00275028 | II | Cediranib | A Phase 2 Study of AZD2171 in Patients With Recurrent Ovarian, Primary Peritoneal Serous or Fallopian Tube Cancer | Cediranib has promising activity but with significant toxicity (hypertension) ORR: 20% pub 2007 |
| Angiogenesis Inhibitors: Multi-targeted RTK | NCT03797326 | II | Lenvatinib, Pembrolizumab | A Multicenter, Open-label Phase 2 Study of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) in Previously Treated Subjects With Selected Solid Tumors (LEAP-005) | Lenvatinib+pembrolizumab demonstrates encouraging efficacy and manageable safety in patients with heavily pretreated OC, including those with prior platinum failure and those with previous bevacizumab exposure ORR: 24% abs Sep 2020 |
| Angiogenesis Inhibitors: Multi-targeted RTK | 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 is tolerable with manageable side effects and shows promising response rates in Pt-R OC, also in patients with rare histologies ORR: 71% (incl. 1 LGS, 2 OCCC, 1 carcinosarcoma) pub 2021 |
| Growth Factor Inhibitors: Gas6 | NCT03639246 | Ib/II | Batiraxcept, Liposomal doxorubicin, Paclitaxel | A Phase 1b/2 Randomized, Controlled Study of AVB-S6-500 in Combination With Pegylated Liposomal Doxorubicin (PLD) or Paclitaxel (Pac) in Patients With Platinum-resistant Recurrent Ovarian Cancer | AVB-S6-500+paclitaxel or liposomal doxorubicin is safe; the combination of AVB-S6-500+paclitaxel is most effective and best response is seen in patients without prior bevacizumab AVB-S6-500+Pac vs AVB-S6-500+PLD: AVB-S6-500+Pac; no prior Bev vs prior Bev: AVB-S6-500+Pac; trough levels above MEC vs below MEC: abs Jun 2021 and poster, pub 2021 |
| Angiogenesis Inhibitors: Gene Therapy | NCT01711970 | I/II | Ofranergene obadenovec, Paclitaxel | A Phase I/II Trial of Multiple Dose VB-111 and Weekly Paclitaxel for the Treatment of Recurrent Platinum-Resistant Müllerian Cancer | Ofranergene Obadenovec+weekly paclitaxel is safe and well tolerated; tumor responses are associated with tumor infiltration of CD8 T-cells ORR (RECIST): 13% (n=15) Ofr (therapeutic dose)+Pac vs Ofr (sub-therapeutic dose, n=4)+Pac: pub 2020 |
| Hormonal Therapy: GR | NCT03776812 | II | nab-Paclitaxel, Relacorilant | A Phase 2, Randomized, Open-Label, 3-arm Study of Relacorilant in Combination With Nab-Paclitaxel for Patients With Recurrent Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer | Intermittent relacorilant+nab-paclitaxel improves PFS and DoR and has a favorable safety profile in recurrent Pt-R and/or Pt-Rf OC patients. OS is improved in patients without primary platinum refractory disease Intermittent Rel+Nab vs Nab: ORR: 35.7 vs 35.8% abs Sept 2021, abs Jun 2022 and presentation |
| 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 BRCA WT patients ORR: 34.6% gBRCA WT: ORR: 31.3% pub 2019 |
| Cell Cycle Inhibitors: Other | NCT02244502; INNOVATE-3 | II | Paclitaxel, TTfields | An Open Label Pilot Study of the NovoTTF-100L(O) System (NovoTTF Therapy) (200 kHz) Concomitant With Weekly Paclitaxel for Recurrent Ovarian Carcinoma | TTfields in combination with weekly paclitaxel is well tolerated and shows encouraging responses ORR: 25% pub 2018 |
| 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 historical results with 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: 61.1% pub 2021 |
| Immunotherapy: Checkpoint Inhibitors/PD-1 | NCT02853318 | II | Cyclophosphamide, Pembrolizumab, Bevacizumab | A Phase II Evaluation of Pembrolizumab in Combination With IV Bevacizumab and Oral Metronomic Cyclophosphamide in the Treatment of Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer | Pembrolizumab+bevacizumab+cyclophosphamide is well tolerated and demonstrates clinical benefit and durable treatment responses ORR: 43.3% pub 2020 |
| Immunotherapy: Checkpoint Inhibitors/PD-1 | NCT02799095; ARTISTRY-1 | I/II | Nemvaleukin alfa, Pembrolizumab | A Phase 1/2 Study of ALKS 4230 Administered Intravenously as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors - ARTISTRY-1 | Pembrolizumab with Nemvaleukin alfa (ALKS 4230) is well tolerated with encouraging clinical benefit ORR: 28.6% (n=14) abs Jun 2021 and poster, abs Mar 2022, abs Jun 2022 and presentation |
| 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 | Pembrolizumab+carboplatin is well-tolerated and active in recurrent Pt-R OC. A ratio of peripheral T-cell exhaustion to radiographic tumor burden may identify patients more likely to benefit from this chemoimmunotherapy ORR: 10.3%; DCR: 63% pub 2021 |
| Immunotherapy: Checkpoint Inhibitors/PD-1 | NCT03596281; PEMBOV | I | Bevacizumab, Liposomal doxorubicin, Pembrolizumab | An Open-label Phase 1 of Pembrolizumab in Combination With Bevacizumab and Pegylated Liposomal Doxorubicin in Patients With Platinum Resistant Epithelial Ovarian Cancer | Pembrolizumab+bevacizumab with or without liposomal doxorubicin is well tolerated and demonstrate durable responses in Pt-R OC patients Bev+Pem: Bev+PLD+Pem: abs Nov 2021, abs Jun 2022 and poster |
| 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: Immune Cell Stimulators/IL-2R | NCT02799095; ARTISTRY-1 | I/II | Nemvaleukin alfa, Pembrolizumab | A Phase 1/2 Study of ALKS 4230 Administered Intravenously as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors - ARTISTRY-1 | Nemvaleukin alfa (ALKS 4230) with pembrolizumab is well tolerated with encouraging clinical benefit ORR: 28.6% (n=14) abs Jun 2021 and poster, abs Mar 2022, abs Jun 2022 and presentation |
| Oncolytic Viruses | NCT02759588; VIRO-15 | Ib/II | Carboplatin, Docetaxel, Gemcitabine, Liposomal doxorubicin, Olvimulogene nanivacirepvec, Paclitaxel, Bevacizumab | Phase 1b & 2 Study With GL-ONC1 Oncolytic Immunotherapy in Patients With Recurrent or Refractory Ovarian Cancer (VIRO-15) | Patients treated with IP 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 Sep 2020, pub 2021 |
| 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 |