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Avutometinib+ Defactinib

Phase 3

Low Grade Serous Ovarian Cancer | Small molecule | Oncology |Verastem, Inc.|Last Updated: Aug 14, 2026

Target and mechanism

Molecular targetMAP2K1, MAP2K2
Target classInhibitor
ModalitySmall molecule

Also known as Avutometinib, avutometinib and sotorasib, avutometinib (VS-6766), avutometinib

Success Probability

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Market & Valuation

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Trial Design

RandomizedACTIVE_CONTROLLEDDMC
Total Trials2
Total Enrollment286

FDA Designations

BREAKTHROUGH_THERAPYORPHAN_DRUG

Clinical trial landscape

Avutometinib+ Defactinib · 3 trials · 7 indications

Phase 3 1Phase 2 2
NCT06072781A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian CancerLow Grade Serous Ovarian Cancer
RECRUITING270 Analytics
PHASE3RECRUITING
A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer
Low Grade Serous Ovarian CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

Progression Free Survival (PFS) per blinded independent central review (BICR)
Up to 24 months

Progression-free survival (PFS) according to RECIST version 1.1, per blinded independent central review (BICR)

Confirmed overall response rate (ORR; partial response [PR] + complete response [CR]
From start of treatment to confirmation of response; 24 weeks

Confirmed overall response rate (ORR; partial response \[PR\] + complete response \[CR\] defined according to Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]) as assessed by the blinded independent central radiology review committee (BICR)

Proportion of Patients with objective response rate
2 years

To evaluate the efficacy of Avutometinib (VS-6766) + defactinib in endometrioid, MOC, HGSOC and solid gynecological cancer patients with RAS/BRAF/NF1 mutations on confirmed overall response rate (ORR; partial response \[PR\] + complete response \[CR\] defined according to RECIST 1.1) as assessed by the investigator.

Secondary Endpoints

Overall Survival (OS)
Up to 5 years
Progression Free Survival (PFS) per investigator assessment
24 months
Objective response rate (ORR)
12 months
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelCROSSOVER
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
avutometinib + defactinibEXPERIMENTALAvutometinib 3.2 mg, PO, twice weekly for 21 days on, 7 days off in a 28-day (4 weeks) cycle in combination with defactinib 200 mg, PO, twice daily for 21 days on, 7 days off in a 28-day(4 week) cycle.
Investigator Choice of Treatment (ICT)ACTIVE_COMPARATORPatients will receive one of the following therapies as determined by the Investigator: * Pegylated liposomal doxorubicin: 40 mg/m2 IV on Day 1 of each 28-day (4 week) cycle. * Paclitaxel: 80 mg/m2 IV on Days 1, 8, and 15 of each 28-day (4 week) cycle. * Anastrozole: 1 mg, PO, once daily of each 28-day (4 week) cycle. * Letrozole: 2.5 mg, PO, once daily of each 28-day (4 week) cycle.
Avutometinib (VS-6766) + DefactinibEXPERIMENTALAvutometinib (VS-6766): will be administered at 3.2 mg orally twice a week Defactinib: will be administered at 200 mg orally twice a day (BID).

Interventions

NameTypeDescription
avutometinibDRUGAvutometinib: administered orally
DefactinibDRUGDefactinib: administered orally
Pegylated liposomal doxorubicinDRUGadministered intravenously
PaclitaxelDRUGadministered intravenously
LetrozoleDRUGadministered orally
AnastrozoleDRUGadministered orally
Avutometinib (VS-6766) + Defactinib (VS-6063)DRUGcombination therapy
Avutometinib (VS-6766) + defactinibDRUGAvutometinib (VS-6766): will be administered at 3.2 mg orally twice a week Defactinib: will be administered at 200 mg orally twice a day (BID). Treatment will be for 3 weeks, followed by a 1-week rest period, in each 4-week (28 day) cycle.
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Eligibility Criteria

Age Range18 Years to N/A
SexFEMALE
Healthy VolunteersNo
Study Sites106

Inclusion Criteria: Patients may be eligible for inclusion in the study if they meet the following criteria: 1. Histologically proven LGSOC (ovarian, fallopian, peritoneal) 2. Documented mutational status of KRAS by a validated tumor-tissue based diagnostic test. 3. Suitable for treatment with at ...

Countries:United StatesAustraliaBelgiumCanadaDenmarkFranceGermanyIrelandItalyJapanNetherlandsNew ZealandPolandSouth KoreaSpainUnited Kingdom
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Recent Changes (Last 90 Days)

LOWAug 14, 2026NCT06072781lastUpdatePostDate: changed
LOWAug 14, 2026NCT06072781lastUpdatePostDate: changed
LOWAug 12, 2026NCT06072781lastUpdatePostDate: changed
LOWAug 12, 2026NCT06072781lastUpdatePostDate: changed
LOWJul 31, 2026NCT06072781lastUpdatePostDate: changed
LOWJul 31, 2026NCT06072781lastUpdatePostDate: changed
LOWJul 27, 2026NCT06072781lastUpdatePostDate: changed
LOWJul 27, 2026NCT06072781lastUpdatePostDate: changed
LOWJul 27, 2026NCT06072781lastUpdatePostDate: changed

Frequently asked questions about Avutometinib+ Defactinib

What is Avutometinib used for?

Avutometinib is an investigational small molecule being studied for the treatment of several cancers, including low grade serous ovarian cancer, glioblastoma multiforme (GBM), endometrioid cancer, and non small cell lung cancer. It is currently in Phase 2 clinical development for these indications.

What does Avutometinib target?

Avutometinib is a kinase inhibitor, as indicated by its '-tinib' suffix. It is being studied both as a monotherapy and in combination with other agents, such as defactinib, for the treatment of various solid tumors.

Who is developing Avutometinib?

Avutometinib is being developed by Verastem, Inc., a biopharmaceutical company. Verastem is listed on the stock exchange under the ticker symbol VSTM.

What phase is Avutometinib in?

Avutometinib is currently in Phase 2 clinical trials. It has received Breakthrough Therapy designation and Orphan Drug designation from the FDA for certain indications, reflecting its potential in treating serious conditions.

What clinical trials is Avutometinib in?

Avutometinib is being evaluated in several clinical trials, including NCT04625270, a Phase 2 study in recurrent low-grade serous ovarian cancer; NCT05798507, an early Phase 1 study in glioblastoma; NCT06630260, a Phase 1 study in malignant brain tumors; and NCT07747506, a continued access study in low-grade serous ovarian cancer.

Is Avutometinib the same as VS-6766?

Yes, Avutometinib is also known as VS-6766. In clinical trials, it is often referred to as avutometinib (VS-6766), particularly when studied in combination with defactinib for conditions like low-grade serous ovarian cancer and glioblastoma.