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avutometinib and sotorasib

Phase 2

Non Small Cell Lung Cancer | Small molecule | Oncology |Verastem, Inc.|Last Updated: Jul 2, 2026

Target and mechanism

Molecular targetMAP2K1, MAP2K2
Target classInhibitor
ModalitySmall molecule

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

Success Probability

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Market & Valuation

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Trial Design

RandomizedCONTROLLED
Total Trials3
Total Enrollment255

FDA Designations

BREAKTHROUGH_THERAPYORPHAN_DRUG

Clinical trial landscape

avutometinib and sotorasib · 3 trials · 6 indications

Phase 2 1Phase 1 2
NCT04620330A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung CancerNon Small Cell Lung Cancer
COMPLETED90 Analytics
PHASE2COMPLETED
A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer
Non Small Cell Lung CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

To determine the optimal regimen, either avutometinib (VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, in KRAS-G12V NSCLC
From start of treatment to confirmation of response; 24 weeks

Confirmed overall response rate per RECIST 1.1

To evaluate the initial efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC
From start of treatment to confirmation of response; 24 weeks

Confirmed overall response rate per RECIST 1.1

To determine efficacy in KRAS-other (non-G12V) NSCLC
From start of treatment to confirmation of response; 24 weeks

Confirmed overall response rate per RECIST 1.1

To determine the efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC
From start of treatment to confirmation of response; 24 weeks

Confirmed overall response rate per RECIST 1.1

Part A: To determine RP2D for avutometinib(VS-6766) in combination with adagrasib
From start of treatment to confirmation of RP2D; 28 days

Assessment of Dose-limiting toxicities (DLTs)

To determine the efficacy of the optimal regimen identified from Part A
From start of treatment to confirmation of response; 16 weeks

Confirmed overall response rate per RECIST 1.1

Part A: To determine RP2D for avutometinib in combination with sotorasib and the Alt-RP2D for avutometinib in combination with sotorasib and defactinib
From start of treatment to confirmation of RP2D; 28 days

Assessment of Dose-limiting toxicities (DLTs)

Part B: To determine the efficacy of the RP2D and/or Alt-RP2D identified from Part A
From start of treatment to confirmation of response; 16 weeks

Confirmed overall response rate per RECIST 1.1

Secondary Endpoints

To characterize the safety and toxicity profile of VS-6766 as a monotherapy and in combination with defactinib in KRAS-MT NSCLC and in BRAF-MT NSCLC
24 weeks
Overall Response Rate per RECIST 1.1 as assessed by Investigator
From start of treatment to confirmation of response; 24 weeks
Duration of Response (DOR)
Time from the first documentation of response to first documentation of progressive disease or death due to any cause, greater than or equal to 6 months
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Arm 1: avutometinib (VS-6766) monotherapyEXPERIMENTALin patients with NSCLC KRAS-G12V tumor
Arm 2: avutometinib (VS-6766) in combination with defactinibEXPERIMENTALin patients with a NSCLC KRAS-G12V tumor
Arm 3: avutometinib (VS-6766) in combination with defactinibEXPERIMENTALin patients with a NSCLC KRAS-other (non-G12V) tumor
Arm 4: avutometinib (VS-6766) in combination with defactinibEXPERIMENTALin patients with a NSCLC BRAF-V600E tumor
Arm 5:avutometinib (VS-6766) in combination with defactinibEXPERIMENTALin patients with a NSCLC BRAF-non-V600E tumor
avutometinib(VS-6766)+adagrasibEXPERIMENTALTo determine the recommended phase 2 dose (RP2D) for VS-6766 in combination with adagrasib in G12C inhibitor exposed patients
avutometinib (VS-6766)+adagrasib RP2DEXPERIMENTALTo determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients
avutometinib (VS-6766)+sotorasibEXPERIMENTALTo determine the recommended phase 2 dose (RP2D) for avutometinib (VS 6766) in combination with sotorasib in KRAS G12C inhibitor naïve and exposed patients
avutometinib (VS-6766)+sotorasib - KRAS G12C inhibitor naïveEXPERIMENTALTo determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor naïve patients
avutometinib (VS-6766)+sotorasib - KRAS G12C inhibitor exposedEXPERIMENTALTo determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor exposed patients
avutometinib (VS-6766)+sotorasib+defactinibEXPERIMENTALTo determine the recommended phase 2 dose (RP2D) for avutometinib (VS-6766) in combination with sotorasib and defactinib in KRAS G12C inhibitor exposed patients
avutometinib (VS-6766)+sotorasib+defactinib - KRAS G12C inhibitor naiveEXPERIMENTALTo determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor naïve patients
avutometinib (VS-6766)+sotorasib+defactinib - KRAS G12C inhibitor exposedEXPERIMENTALTo determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor exposed patients

Interventions

NameTypeDescription
avutometinib (VS-6766)DRUGMonotherapy
avutometinib (VS-6766) and DefactinibDRUGCombination therapy
avutometinib (VS-6766) and adagrasibDRUGThe RP2D of VS-6766 + adagrasib determined in Part A will be used in Part B dose expansion
avutometinib and sotorasibDRUGThe RP2D of avutometinib + sotorasib determined in Part A will be used in Part B dose expansion
avutometinib and sotorasib and defactinibDRUGThe RP2D of avutometinib + sotorasib + defactinib determined in Part A will be used in Part B dose expansion
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites45

Inclusion Criteria: * Male or female subjects ≥ 18 years of age * Histologic or cytologic evidence of NSCLC * Known KRAS or BRAF mutation * The subject must have received appropriate prior therapy * Measurable disease according to RECIST 1.1 * An Eastern Cooperative Group (ECOG) performance status ...

Countries:United StatesFranceGermanyItalySpainBelgiumNetherlandsUnited Kingdom
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Competitive Landscape -Non-Small Cell Lung Cancer 389 trials (matched to "Non Small Cell Lung Cancer")

Recent Changes (Last 90 Days)

MEDIUMAug 2, 2026NCT05375994TRIAL_REMOVED: changed
MEDIUMAug 2, 2026NCT05375994TRIAL_REMOVED: changed
MEDIUMAug 2, 2026NCT05375994TRIAL_REMOVED: changed
MEDIUMAug 2, 2026NCT05375994TRIAL_REMOVED: changed
HIGHJul 2, 2026NCT05375994Status: ACTIVE_NOT_RECRUITING → COMPLETED
HIGHJul 2, 2026NCT05375994Status: ACTIVE_NOT_RECRUITING → COMPLETED
HIGHJul 2, 2026NCT05375994Status: ACTIVE_NOT_RECRUITING → COMPLETED

Frequently asked questions about avutometinib and sotorasib

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.