Drug Class: Signaling Pathway Inhibitors

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

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

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