Clinical Situation: Platinum-Resistant/Refractory Recurrence

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

1 Prior Therapy 2 Prior Therapies 3 Prior Therapies 4 Prior Therapies 5 Prior Therapies 6 Prior Therapies Prior Therapies Not Reported

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%
PFS: 3.1 vs 3.6 months

pub 2007

Chemotherapy Study 30-49 III Liposomal doxorubicin, Topotecan 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%
PFS: 2.3 vs 3.4 months

pub 2001

Chemotherapy NCT00023907 II Paclitaxel Prescribing Information 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 platinum-resistant and platinum-refractory 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%*
PFS: 6.7 vs 3.4 months*

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 gBRCA MUT patients

ORR: 30%
PFS: 5.5 months

pub 2016

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 Apr 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%
PFS: 5.7 months

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%
PFS: 2.1 months

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%
PFS: 2.9 months

pub 2009

Chemotherapy Rose (2003) CisPt+Gem II Cisplatin, Gemcitabine Phase II study of cisplatin plus gemcitabine in platinum-resistant and platinum-refractory ovarian cancer

The combination of cisplatin+gemcitabine is active in platinum-resistant and platinum-refractory patients

ORR: 42.9%
PFS: 6 months

pub 2003

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%
PFS: 4.4 months
OS: 10.7 months

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%
PFS: 3 months

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%
PFS: 4.4 months

pub 2010

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%
PFS: 5.8 months

pub 2015

DNA Damage Repair Pathway Inhibitors:PARP NCT02345265 II Cediranib, Olaparib A Phase 2 Study of Olaparib and Cediranib for the Treatment of Recurrent Ovarian Cancer

Olaparib+cediranib combination shows activity in Pt-R patients

ORR: 20%

gBRCA WT:
ORR: 18%

gBRCA MUT:
ORR: 60% (n=5)

abs Jun 2018

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 promising activity in late-line treatment setting

BRCA MUT:
ORR: 27%

HRD-positive (incl. BRCA MUT):
ORR: 10%

pub 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 combination in Pt-R/Pt-Rf patients 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

The combination of pamiparib and tislelizumab was generally well tolerated and associated with antitumor responses in both BRCA WT and BRCA MUT patients

ORR: 22%
DCR: 50%

pub 2019

Antibody 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%
PFS: 6.7 vs 3.9 months

pub 2017; abs Jun 2017

Antibody 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%
PFS: 5.5 months

abs Jun 2018

Antibody Drug Conjugates: Other 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 signs of anti-tumor activity

ORR: 16%

abs Jun 2019

Antibody Drug Conjugates: Other 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

Manageable safety profile and encouraging anti-tumor activity in heavily pretreated patients

ORR: 13% (n=15)

abs Jun 2019

Angiogenesis Inhibitors: VEGF NCT02606305 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

Encouraging activity of bevacizumab+mirvetuximab soravtansine combination in FRalpha-positive patients

ORR: 39%
PFS: 6.9 months

abs Jun 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 combination in heavily pretreated patients

ORR: 42%
PFS: 5.4 months

abs Oct 2018

Angiogenesis Inhibitors: VEGFR/PDGFR 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 and weekly paclitaxel combination shows promising response rates

ORR: 71%
PFS: 14 months

abs Mar 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 in gBRCA WT patients

ORR: 36%
PFS: 7.2 months

gBRCA WT:
ORR: 35%

pub 2019

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%
DCR (6 months): 27%

abs Jun 2016; Jun 2017

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%
PFS: 7.5 months

pub 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%
PFS: 5.3 months

pub 2016

Cell Cycle Inhibitors: Wee1 NCT02101775 II Adavosertib, Gemcitabine A Randomized Placebo-Controlled Phase II Trial Comparing Gemcitabine Monotherapy to Gemcitabine in Combination With AZD 1775 (MK 1775) in Women With Recurrent, Platinum Resistant Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers

Addition of adavosertib to gemzar improves ORR, PFS and OS in platinum-resistant patients
Gem+Ada vs Gem:

ORR: 25 vs 7%
PFS: 4.6 vs 3 months
OS: 11.4 vs 7.2 months

abs Jun 2019

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)
PFS: 5.4 months

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 combination with acceptable safety profile

ORR: 19%
DCR: (6 months): 42%

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%
DCR: 45%
PFS: 3.5 months

pub 2015

Immunotherapy: Checkpoint Inhibitors/PD-1 NCT02606305 Ib/II 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%
PFS: 4.2 months

abs Mar 2018; Oct 2018

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%
PFS: 4.6 months

abs Jun 2019

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: 9.6%
DCR: 52.0%
PFS: 2.6 months

pub 2019

Immunotherapy: Checkpoint Inhibitors/PD-1 NCT02054806 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%
DCR: 35%
PFS: 1.9 months

abs Jun 2017

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 the combination of avelumab and 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 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%
PFS: 5.5 months

abs Oct 2018

*Statistically significant result

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