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 2.5 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; 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%
PFS: 2.3 vs 3.4 months

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%*
PFS: 6.7 vs 3.4 months*

pub 2014; 2015

Angiogenesis Inhibitors: VEGF UMIN000017247; JGOG3023 II Bevacizumab, Gemcitabine, Liposomal doxorubicin, Paclitaxel, Topotecan 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%
PFS: 4.0 vs 3.1 months*
OS: 15.3 vs 11.3 months

pub 2021

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%
PFS: 5.5 months

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 platinum resistant patients in late-line treatment setting

BRCA MUT:
ORR: 27%

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%
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

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 platinum resistant patients in late-line treatment setting

HRD+ (incl. BRCA MUT):
ORR: 10%

HRD+ (excl. BRCA MUT):
CBR: 14%

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%
PFS: 4.4 months
OS: 10.7 months

pub 2007

Angiogenesis Inhibitors: VEGF Retrospective Study: Bevacizumab and Cyclophosphamide 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

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%*
PFS: 6.7 vs 4.4 months*
OS: 17.1 vs 10.1 months*

pub 2018

Drugs in Clinical Development
Chemotherapy NCT03093155 II Bevacizumab, Ixabepilone A Randomized Phase II Evaluation of Weekly Ixabepilone With or Without Biweekly Bevacizumab in Recurrent or Persistent Platinum-resistant/Refractory Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancers

Ixabepilone+bevacizumab is a well-tolerated, effective combination for treatment of platinum/taxane resistant ovarian cancer that extends both PFS/OS relative to ixabepilone monotherapy and prior receipt of bevacizumab should not preclude use of ixabepilone+bevacizumab

Ixa+Bev vs Ixa:
ORR: 33 vs 8%*
PFS: 5.5 vs 2.2 months*
OS: 10.0 vs 6.0 months*

abs Mar 2021

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%
PFS: 6 months

pub 2003

Chemotherapy UMIN000004449 II Gemcitabine, Irinotecan Phase I/II Trial of Gemcitabine and Irinotecan in Patients with Platinum Refractory and Resistant Ovarian cancer

Tailored-dose chemotherapy with gemcitabine+irinotecan is effective and well tolerated in patients with platinum-refractory/resistant ovarian cancer

ORR: 20%
PFS: 6.2 months
OS: 16.8 months

pub 2021

DNA Damage Repair Pathway Inhibitors: PARP NCT01891344; ARIEL2 II Rucaparib A Phase 2, Open-Label Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)

In platinum resistant patients rucaparib is most effective in patients that have BRCA1/2 mutations

BRCA MUT vs BRCA WT LOH high vs BRCA WT LOH low:

ORR: 23.4 vs 4.1 vs 5.4%
PFS: 7.2 vs 1.9 vs 1.8 months

pub 2021

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

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%
PFS: 5.1 months

abs May 2020 and poster

DNA Damage Repair Pathway Inhibitors: PARP NCT03314740; BAROCCO II Olaparib, Cediranib 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:
PFS: 5.8 vs 3.8 vs 2.1 months

abs Oct 2019

DNA Damage Repair Pathway Inhibitors: PARP NCT03574779; OPAL II Bevacizumab, Niraparib, Dostarlimab Phase 2 Multicohort Study to Evaluate the Safety and Efficacy of Novel Treatment Combinations in Patients With Recurrent Ovarian Cancer

Triplet therapy with niraparib, dostarlimab, and bevacizumab is tolerable and demonstrates clinical activity in patients with BRCA WT platinum resistant ovarian cancer without HRR gene mutations

ORR: 17.9%
DCR: 76.9%
PFS: 7.6 months

w/ prior Bev: ORR: 6%
w/o prior Bev: ORR: 27%

abs Mar 2021

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 in platinum resistant patients independent of BRCA status, HRD status and PD-L1 expression

ORR: 21%

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:
ORR: 22%
DCR: 50%

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 increases PFS without additional toxicity, the benefit was observed mainly in patients with platinum-free interval less than 3 months

Ber+Gem vs Gem:

PFS: 5.7 vs 3.7 months*

pub 2020, pub 2021

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%*
PFS: 4.8 vs 3.3 months*

FRalpha high (PS2+ scoring method):

ORR: 26 vs 6%*
PFS: 5.6 vs 3.2 months*
OS: 16.4 vs 11.4 months*

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 platinum resistant ovarian cancer

ORR: 32.4%

press release Nov 2021

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%
PFS: 9.7 months

abs Jun 2021 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: 40.9%
PFS: 7.5 months

abs Jun 2021 and poster

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%
CBR: 55%
PFS: 7.2 months

abs Jun 2021 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: CD166 NCT03149549 I/II Praluzatamab ravtansine 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)
DCR: 66.7% (2PR, 10SD)

abs May 2020 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 platinum resistant ovarian cancer

ORR: 23%
DCR: 72%

NaPi2b High (TPS≥75):
ORR: 34%
DCR: 87%

abs Oct 2020 and presentation, press release Jan 2021, press release Nov 2021

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 platinum resistant patients, including those treated with topotecan and/or avastin

ORR: 21%
DCR: 63.2%

pub 2017

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%
CBR: 33.3%
PFS: 7.7 months

pub 2019

Angiogenesis Inhibitors: VEGF 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

Bevacizumab+liposomal doxorubicin+pembrolizumab is well tolerated and demonstrate durable responses in platinum resistant ovarian cancer patients

Bev+Pem:
ORR: 26.3%
DCR: 78.9%

Bev+PLD+Pem:
ORR: 32%
DCR: 74%
CBR: 53%

abs Jun 2021 and poster, abs Nov 2021

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%
PFS: 7.3 months

abs Mar 2020, poster Oct 2021

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%
PFS: 5.2 months

pub 2007

Angiogenesis Inhibitors: Multi-targeted RTK NCT03797326 II Pembrolizumab, Lenvatinib 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 ovarian cancer, including those with prior platinum failure and those with previous bevacizumab exposure

ORR: 24%

abs Sep 2020

Angiogenesis Inhibitors: Multi-targeted RTK Retrospective Study: Pazopanib and Oral Cyclophosphamide II Cyclophosphamide, Pazopanib Pazopanib and Oral Cyclophosphamide in Women With Platinum-Resistant or -Refractory Epithelial Ovarian Cancer

Pazopanib+cyclophosphamide is a well-tolerated regimen with clinically relevant benefit in patients with platinum-resistant or -refractory ovarian cancer

ORR: 45%
PFS: 5.5 months
OS: 9.5 months

pub 2020

Angiogenesis Inhibitors: Multi-targeted RTK NCT02788708 I Paclitaxel, Lenvatinib 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 platinum resistant ovarian cancer, also in patients with rare histologies

ORR: 71% (incl. 1 LGS, 2 clear cell, 1 carcinosarcoma)
PFS: 7.2 months

pub 2021

Angiogenesis Inhibitors: Multi-targeted RTK NCT03666143 I Tislelizumab, Sitravatinib 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: 26%
PFS: 4.1 months

abs Apr 2021 and presentation

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:
ORR: 36.8 vs 16.0%
DCR: 68.4 vs 60.0%
PFS: 3.6 vs 3.6 months

AVB-S6-500+Pac; no prior Bev vs prior Bev:
ORR: 66.7 vs 10.0%
DCR: 88.9 vs 60%
PFS: 7.7 vs 2.8 months
OS: 19.3 vs 9.2 months

AVB-S6-500+Pac; trough levels above MEC vs below MEC:
ORR: 50 (n=10) vs 22% (n=9)
PFS: 7.5 vs 2.8 months

abs Jun 2021and poster, pub 2021

Signaling Pathway Inhibitors: PI3K-AKT-mTOR/AKT NCT01653912 I/II Afuresertib, Carboplatin, Paclitaxel An Open-Label Phase I/II Study of GSK2110183 in Combination With Carboplatin and Paclitaxel in Subjects With Platinum-Resistant Ovarian Cancer

Afuresertib mediated AKT kinase inhibition in combination with carboplatin+paclitaxel demonstrates promising efficacy in platinum resistant ovarian cancer

ORR: 32.1%
PFS: 7.1 months

pub 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 BRCA WT patients

ORR: 34.6%
PFS: 7.2 months

gBRCA WT: ORR: 31.3%
gBRCA MUT: ORR: 33.3% (n=9)
BRCA WT: ORR: 33.3% (n=12)
BRCA MUT: ORR: 30.8% (n=13)

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 platinum resistant ovarian cancer but with substantial toxicity

ORR: 32.1%

abs Jun 2013 and poster

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%
PFS: 8.9 months

pub 2018

Immunotherapy: Checkpoint Inhibitors/PD-1 JapicCTI-153004; NINJA III Gemcitabine, Liposomal doxorubicin, Nivolumab Multicenter, open-label, randomized study in patients with ovarian cancer(ONO-4538-23)

Nivolumab does not improve OS compared with gemcitabine/liposomal doxorubicin in patients with platinum resistant ovarian cancer

PFS: 2.0 vs 3.8 months
OS: 10.1 vs 12.1 months

pub 2021

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%
PFS: 6.7 months
OS: 13.4 months

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%
PFS: 6.2 months

pub 2021

Immunotherapy: Checkpoint Inhibitors/PD-1 NCT02853318 II Bevacizumab, Cyclophosphamide, Pembrolizumab 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%
DCR: 95%
PFS: 7.6 months

pub 2020

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: 26.1%
CBR: 52.2%

pub 2020

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 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 platinum-resistant ovarian cancer. 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%
PFS: 4.6 months
All 7 PD-L1+ patients achieved PR or SD

pub 2021

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%
DCR: 35%
PFS: 1.9 months

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 (PLD) compared to avelumab or PLD alone

Ave+PLD vs Ave vs PLD:

ORR: 13.3 vs 3.7 vs 4.2%
PFS: 3.7 vs 1.9 vs 3.5 months
OS: 15.7 vs 11.8 vs 13.1 months

pub 2021

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%
PFS: 5.5 months
OS: 17.6 months

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%
DCR: 52.0%
PFS: 2.6 months

pub 2019

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 platinum resistant and/or platinum refractory ovarian cancer patients

Continuous Rel+Nab vs Intermittent Rel+Nab vs Nab:

ORR: 35.2 vs 35.7 vs 35.8%
PFS: 5.29 vs 5.55* vs 3.76 months
DoR: 3.79 vs 5.55* vs 3.65 months

abs Sept 2021

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-Naive 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; VIRO-15 Ib/II Bevacizumab, Docetaxel, Gemcitabine, Liposomal doxorubicin, Olvimulogene nanivacirepvec, 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:
ORR: 9% (n=11)
DCR: 73% (n=11)

Olvi-Vec+CarboPt-based therapy +/- Bev:
ORR: 54%
DCR: 88%
PFS: 11.0 months

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%
OS: 26.5 months

pub 2015

*Statistically significant result

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