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Also known as avutometinib and sotorasib, avutometinib (VS-6766)
Avutometinib · 5 trials · 10 indications
Treatment exposure will be summarized descriptively for participants receiving continued treatment with avutometinib in combination with defactinib after completion of Study VS-6766-201 (RAMP-201).
To determine the efficacy of combination defactinib and avutometinib in patients with metastatic diffuse gastric cancer (DGC) as measured by 6-month progression-free survival (PFS) rate. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Confirmed overall response rate per RECIST 1.1
Confirmed overall response rate per RECIST 1.1
Confirmed overall response rate per RECIST 1.1
Confirmed ORR defined according to RECIST 1.1
To identify the incidence, nature and severity of adverse events and laboratory abnormalities, with severity determined according to NCI CTCAE v5.0
Antitumour activity will be defined on the basis of the following outcomes. If any of the following occur, patients will be considered to have clinically benefitted: For relapsed GBM: Achievement of overall response of CR or PR per Response Assessment in Neuro-Oncology (RANO) within 6 months or Free of disease progression or death at 6 months For front line unmethylated GBM (MRD): • Progression-free survival (PFS)
Antitumour activity will be defined on the basis of the following outcomes: Progression-free survival (PFS), defined as the time from enrolment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RANO Overall survival (OS), defined as the time from enrolment to death from any cause
Defactinib concentration will be measured in a sample of the glioblastoma, brain around the glioblastoma, and in a serum sample from each subject receiving Defactinib. Descriptive statistics, such as mean and standard deviation, will be generated with these results. Concentration will be compared between dose levels within study drug using two-sample t-tests or non-parametric equivalents such as Mann Whitney U tests.
VS-6766 concentration will be measured in a sample of the glioblastoma, brain around the glioblastoma, and in a serum sample from each subject receiving VS-6766. Descriptive statistics, such as mean and standard deviation, will be generated with these results. Concentration will be compared between dose levels within study drug using two-sample t-tests or non-parametric equivalents such as Mann Whitney U tests.
Will be assessed by quantification of the recognized side effects of this agent including fatigue, nausea, diarrhea, vomiting, hyperbilirubinemia, decreased appetite, peripheral edema, dizziness, and headache and by monitoring for new or undescribed adverse events. Summary statistics will include frequencies and percentages of adverse events.
Will be assessed by quantification of the recognized side effects of this agent including rash, creatine phosphokinase elevation, visual disturbances, hypoalbuminemia, and fatigue and by monitoring for new or undescribed adverse events. Summary statistics will include frequencies and percentages of adverse events.
| Arm | Type | Description |
|---|---|---|
| Continued Treatment of Avutometinib + Defactinib | EXPERIMENTAL | To provide continued treatment with avutometinib in combination with defactinib for participants with recurrent LGSOC who are deriving continued clinical benefit after completion of the VS-6766-201 (RAMP-201) study |
| Avutometinib & Defactinib | EXPERIMENTAL | Avutometinib: Study participants will receive Avutometinib 3.2mg orally two times per week for three weeks in a row followed by one week of rest Defactinib: Study participants will receive Defactinib 200mg twice daily for three weeks in a row followed by one week of rest |
| Part A | EXPERIMENTAL | To determine the optimal regimen, either avutometinib(VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, for subsequent evaluation for efficacy in the Expansion Phase (Part B) |
| Part B | EXPERIMENTAL | To determine the efficacy of the optimal regimen identified from Part A |
| Part C: | EXPERIMENTAL | To evaluate additional efficacy parameters for the optimal regimen identified in Part A. |
| Part D | EXPERIMENTAL | To evaluate additional efficacy parameters for a lower dose of avutometinib in combination with defactinib |
| Phase 1b | EXPERIMENTAL | The Phase 1b will evaluate the safety and tolerability of combination of avutometinib and defactinib and determine its preliminary antitumour activity when administered at the recommended Phase 2 dose (RP2D) in patients with molecularly defined malignant brain tumours. |
| Phase 2 | EXPERIMENTAL | The Phase 2 part of the study will determine the antitumour activity of investigational agents administered at the RP2D in patients with molecularly defined malignant brain tumours. Avutometinib and defactinib may be administered in combination with temozolomide (TMZ). |
| Arm I (Defactinib) | EXPERIMENTAL | Patients receive 1 dose of defactinib PO while on study, prior to planned tumor resection. Patients undergo blood collection and donate resected tumor tissue while on study. |
| Arm II (Avutometinib) | EXPERIMENTAL | Patients receive 1 dose of avutometinib PO while on study, prior to planned tumor resection. Patients undergo blood collection and donate resected tumor tissue while on study. |
| Name | Type | Description |
|---|---|---|
| avutometinib + defactininb combination | DRUG | Avutometinib: administered orally twice a week Defactinib: administered orally twice daily |
| Avutometinib | DRUG | 3.2mg orally |
| Defactinib | DRUG | 200 mg orally |
| avutometinib (VS-6766) | DRUG | avutometinib (VS-6766) monotherapy |
| avutometinib (VS-6766) and defactinib | DRUG | avutometinib (VS-6766) and defactinib combination |
| Temozolomide | DRUG | Temozolomide will be supplied as 5, 20, 100, 140, 180 or 250 mg hard capsules. |
| Biospecimen Collection | PROCEDURE | Undergo blood and tissue sample collection |
Inclusion Criteria: 1. Currently active on VS-6766-201(RAMP-201) study while receiving avutometinib in combination with defactinib, have not required prior permanent discontinuation of avutometinib plus defactinib. Any active dose hold from the RAMP-201 study should be ≤ 28 days at the time of Scre...
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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.
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.
Avutometinib is being developed by Verastem, Inc., a biopharmaceutical company. Verastem is listed on the stock exchange under the ticker symbol VSTM.
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.
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.
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.