Drug Class: Signaling Pathway Inhibitors

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

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

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