Drug Class: Signaling Pathway Inhibitors

Integrin-FAK Inhibitors: FAK

Treatment given for recurrence occurring at any time after 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

3 Prior Therapies 4 Prior Therapies

PI3K/AKT/mTOR Pathway Inhibitors: PI3Kalpha

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

3 Prior Therapies

PI3K/AKT/mTOR Pathway Inhibitors: pan-PI3K

Treatment given for recurrence occurring at any time after 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

Prior Therapies Not Reported

PI3K/AKT/mTOR Pathway Inhibitors: AKT

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

4 Prior Therapies

PI3K/AKT/mTOR Pathway Inhibitors: mTOR

Neo adjuvant (before surgery) and first-line treatment with/without extended (maintenance) treatment

Progression Free Survival (months)

Median length of time before the cancer comes back or gets worse

Overall Survival (months)

The length of time where half the patients in the study are still alive

No Prior Therapies

Platinum-Sensitive (Pt-S): Treatment given for recurrence occurring 6 months or more after 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

Prior Therapies Not Reported

Partially Pt-Sensitive/Resistant: Treatment given for recurrence occurring 6-12 months or less than 6 months after 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

2 Prior Therapies

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

Prior Therapies Not Reported

RAS/RAF/MAPK Pathway Inhibitors: RAF/MEK

Treatment given for recurrence occurring at any time after 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

4 Prior Therapies

RAS/RAF/MAPK Pathway Inhibitors: MEK

Treatment given for recurrence occurring at any time after 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

3 Prior Therapies Prior Therapies Not Reported

JAK/STAT Inhibitors: STAT3

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

4 Prior Therapies

Integrin-FAK Inhibitors: FAK

Treatment given for recurrence occurring at any time after last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
NCT01778803 I Defactinib, Paclitaxel A Phase I/Ib Study of Paclitaxel in Combination With VS-6063, a Focal Adhesion Kinase Inhibitor, in Subjects With Advanced Ovarian Cancer

Defactinib + weekly paclitaxel is well tolerated and showed promising activity

ORR: 18.2%
DCR: 63.6%

abs May 2014 and poster

NCT03875820 I Defactinib, VS-6766 FRAME: A Phase I Trial of the Combination of VS-6063 (FAK Inhibitor) and RO5126766 (CH5126776) (a Dual RAF/MEK Inhibitor) in Patients With Advanced Solid Tumours

VS-6766 (CH5127677)+defactinib shows promising clinical activity in patients with low grade serous ovarian cancer including those who have been previously treated with a MEK inhibitor

ORR: 46%
PFS: 23 months
11 KRAS MUT: ORR: 64%
9 KRAS WT: ORR: 44%

abs Apr 2021 and poster, abs Sep 2021

PI3K/AKT/mTOR Pathway Inhibitors: PI3Kalpha

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.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
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

PI3K/AKT/mTOR Pathway Inhibitors: pan-PI3K

Treatment given for recurrence occurring at any time after last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
NCT01363232 I Binimetinib, Buparlisib A Phase Ib, Open-label, Multi-center, Dose-escalation and Expansion Study of an Orally Administered Combination of BKM120 Plus MEK162 in Adult Patients With Selected Advanced Solid Tumors

Buparlisib+binimetinib shows encouraging efficacy in RAS/RAF MUT ovarian cancer patients, but with significant toxicity

ORR: 27.8%
DCR: 61.1%
PFS: 3.7 months

Pub 2020

PI3K/AKT/mTOR Pathway Inhibitors: AKT

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.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
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

PI3K/AKT/mTOR Pathway Inhibitors: mTOR

Neo adjuvant (before surgery) and first-line treatment with/without extended (maintenance) treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
NCT01579812 II Carboplatin, Metformin, Paclitaxel A Phase II Evaluation of Metformin, Targeting Cancer Stem Cells for the Prevention of Relapse in Patients With Stage IIC/III/IV Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

Metformin treatment before surgery and added to first-line chemotherapy is well tolerated and is associated with a better than expected OS, particularly in patients with stage II-III disease

PFS: 18.0 months
OS: 57.9 months

pub 2020

First-line treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
IRCT2016- 022726788N1 II Carboplatin, Metformin, Paclitaxel Evaluation of the clinical efficacy of adding metformin to chemotherapy regimen for patients with ovarian cancers

Improved RFS with addition of metformin to carboplatin+paclitaxel in stage I-III patients

CarboPt+Pac+Met vs CarboPt+Pac:

RFS: 48.0 vs 25.7 months

pub 2018

Platinum-Sensitive (Pt-S): Treatment given for recurrence occurring 6 months or more after last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
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 sensitive ovarian cancer but with substantial toxicity

ORR: 24%

abs Jun 2013 and poster

NCT01031381 II Bevacizumab, Everolimus Phase II Study of RAD001 and Bevacizumab in Recurrent Ovarian, Peritoneal, and Fallopian Tube Cancer An Investigator-initiated, Single-institution Trial at Magee-Womens Hospital

Everolimus+bevacizumab does not improve responses compared to bevacizumab alone in Pt-S ovarian cancer patients, but selected patients with alterations in the PI3K/mTOR pathway may have benefit

ORR: 16.7%

pub 2020

Partially Pt-Sensitive/Resistant: Treatment given for recurrence occurring 6-12 months or less than 6 months after last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
NCT00429793 II Temsirolimus A Phase II Evaluation of CCI-779 (Temsirolimus, NCI-Supplied Agent, NSC #683864, IND #61010) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma

Temsirolimus has modest activity, but phase III not warranted in unselected patients; CCND1 positivity associated with longer PFS

ORR: 9.3%
PFS: 3.2 months
OS: 11.6 months

pub 2011

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.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
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

NCT01031381 II Bevacizumab, Everolimus Phase II Study of RAD001 and Bevacizumab in Recurrent Ovarian, Peritoneal, and Fallopian Tube Cancer An Investigator-initiated, Single-institution Trial at Magee-Womens Hospital

Everolimus+bevacizumab does not improve responses compared to bevacizumab alone in Pt-R ovarian cancer patients, but selected patients with alterations in the PI3K/mTOR pathway may have benefit

ORR: 11.1%
2 clear cell w/ PI3K pathway and ARID1A alterations (1PR, 1SD > 9 months)

pub 2020

Treatment given for recurrence occurring at any time after last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
NCT02283658 II Everolimus, Letrozole A Phase 2 Trial of Letrozole and Everolimus in Relapsed Hormone Receptor Positive Ovarian, Fallopian Tube or Primary Peritoneal Carcinomas

Everolimus+letrozole combination shows promising results in ER-positive ovarian cancer

PFS: 3.9 months
OS: 13.0 months

pub 2017

PI3K/AKT/mTOR Pathway Inhibitors: TORC 1/2

Treatment given for recurrence occurring at any time after last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
NCT02193633 I Paclitaxel, Vistusertib TAX-TORC: A Phase I Multi-centre Trial of the Combination of AZD2014 (Dual mTORC1 and mTORC2 Inhibitor) and Weekly Paclitaxel in Patients With Solid Tumours

Vistusertib+paclitaxel combination has promising anti-tumor activity

25 evaluable ovarian:
ORR: 52%
PFS: 5.8 months

pub 2018

RAS/RAF/MAPK Pathway Inhibitors: RAF/MEK

Treatment given for recurrence occurring at any time after last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
NCT03875820 I Defactinib, VS-6766 FRAME: A Phase I Trial of the Combination of VS-6063 (FAK Inhibitor) and RO5126766 (CH5126776) (a Dual RAF/MEK Inhibitor) in Patients With Advanced Solid Tumours

VS-6766 (CH5127677)+defactinib shows promising clinical activity in patients with low grade serous ovarian cancer including those who have been previously treated with a MEK inhibitor

ORR: 46%
PFS: 23 months
11 KRAS MUT: ORR: 64%
9 KRAS WT: ORR: 44%

abs Apr 2021 and poster, abs Sep 2021

RAS/RAF/MAPK Pathway Inhibitors: MEK

Treatment given for recurrence occurring at any time after last platinum-based treatment

For more detailed information, please click on the clinical trial ID number.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
NCT01849874; MILO/ENGOT-OV11 III Binimetinib, Liposomal doxorubicin, Paclitaxel, Topotecan A Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Low-grade Serous Ovarian, Fallopian Tube or Peritoneal Cancer

Binimetinib shows activity in low grade serous ovarian cancer, but chemotherapy responses were higher than expected; higher response rates and longer PFS were seen in patients treated with binimetinib who harbored MAPK pathway mutations, most commonly in KRAS

Bin vs TPC (Pac, PLD or Top):

ORR: 24 vs 24%
PFS: 11.2 vs 14.1 months
OS: 25.3 vs 20.8 months

pub 2020, abs Jun 2021 and poster

NCT02101788 III Letrozole, Liposomal doxorubicin, Paclitaxel, Tamoxifen, Topotecan, Trametinib A Randomized Phase II/III Study to Assess the Efficacy of Trametinib (GSK 1120212) in Patients With Recurrent or Progressive Low-Grade Serous Ovarian Cancer or Peritoneal Cancer

In low grade serous ovarian cancer, trametinib is associated with significantly improved ORR and PFS compared to standard of care

Tra vs TPC (Let, Pac, PLD, Tam or Top):

ORR: 26.2 vs 6.2%
PFS: 13.0 vs 7.2  months

abs Oct 2019

NCT00551070 II Selumetinib A Phase II Trial of AZD6244 (NSC# 748727) in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary or Peritoneum

Selumetinib has promising activity in patients with low grade serous ovarian cancer; no significant correlation of response with BRAF or RAS mutations, but analysis performed on primary tumor specimens

ORR: 15.4%
PFS: 11.0 months

pub 2013

NCT01363232 I Binimetinib, Buparlisib A Phase Ib, Open-label, Multi-center, Dose-escalation and Expansion Study of an Orally Administered Combination of BKM120 Plus MEK162 in Adult Patients With Selected Advanced Solid Tumors

Binimetinib+buparlisib shows encouraging efficacy in RAS/RAF MUT ovarian cancer patients, but with significant toxicity

ORR: 27.8%
DCR: 61.1%
PFS: 3.7 months

Pub 2020

JAK/STAT Inhibitors: STAT3

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.

Trial ID # Phase Drugs Clinical Trial Title Key Conclusion and Results
Drugs in Clinical Development
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

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