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
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
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 | ||||
| NCT04625270: RAMP 201 | II | Avutometinib, Defactinib | A Phase 2 Study of Avutometinib (VS-6766) (Dual RAF/MEK Inhibitor) Alone and In Combination With Defactinib (FAK Inhibitor) in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) | The combination of avutometinib with defactinib yields encouraging response rates with a well tolerated safety profile in women with heavily pretreated recurrent LGSOC regardless of KRAS status and with prior MEK inhibitor treatment Avu+Def vs Avu: ORR: 45 vs 10% KRAS MUT: KRAS WT: abs Jun 2023 and poster, abs Mar 2024 |
| NCT03875820; FRAME | I | Avutometinib, Defactinib | FRAME: A Phase I Trial of the Combination of Defactinib (VS-6063) (FAK Inhibitor) and VS-6766 (RO5126766) (CH5126776) (a Dual RAF/MEK Inhibitor) in Patients With Advanced Solid Tumours | Avutometinib (VS-6766)+defactinib shows promising clinical activity in patients with LGSOC including those who have been previously treated with a MEK inhibitor ORR: 46% 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 LGSOC, 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% Bin: w/ MAPK pathway alterations vs w/o MAPK pathway alterations: pub 2020, 2023 |
| NCT02101788; GOG-281/LOGS | 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 LGSOC, 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%* pub 2022 |
| 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% 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% Pub 2020 |