Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
VS-6766 · 3 trials · 8 indications
Determine maximum tolerated dose (MTD) of VS-6766 in combination with abemaciclib and fulvestrant using Bayesian Optimal Interval Design
Determine Recommended Phase II Dose (RP2D) of VS-6766 in combination with abemaciclib and fulvestrant using Bayesian Optimal Interval Design
The primary endpoint in phase II is assessment of the clinical benefit rate (CBR; complete response + partial response + stable disease for \>/=24 weeks)
Area under plasma Concentration (AUC) 0 to t
Area under plasma Concentration (AUC) from 0-120 minutes
Area under plasma Concentration (AUC) from zero to infinity
Area under plasma Concentration (AUC) extrapolated
Cmax for VS-6766 administered with and without food.
absorption lag-time (Tlag)
time of Maximum concentration (Tmax)
Elimination rate (Kel)
concentration Half-life (T1/2)
Oral Clearance (CL/F)
Apparent Volume of Distribution (Vz/F) for VS-6766 administered with and without food.
To determine the maximum dose at which no more than 1 of 6 patients at the same dose level experience a drug related toxicity (DLT) as specified in the protocol.
To assess the safety and toxicity profile of VS-6766 and Defactinib. To determine causality and grading severity of each adverse event by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
| Arm | Type | Description |
|---|---|---|
| Phase 1 Dose Escalation | EXPERIMENTAL | During 28 day/4 week study cycle, participants will receive: * VS-6766 2x weekly for 3 out of the 4 week cycle * Abemaciclib 2x daily * Fulvestrant on day 1 of each study cycle (and day 15 of cycle 1 only) |
| Phase 2 Dose Expansion | EXPERIMENTAL | Participants will receive VS-6766 with abemaciclib and fulvestrant at the recommended phase II doses determined in the phase I portion of the study. |
| Treatment A | ACTIVE_COMPARATOR | 4.0 mg VS-6766, following an overnight fast of at least 10 hours |
| Treatment B | ACTIVE_COMPARATOR | 4.0 mg VS-6766, administered 30 minutes after the start of a high-fat/high-calorie meal breakfast |
| Dose Escalation Phase | EXPERIMENTAL | Escalating doses of VS-6766 (RO5126766) and Defactinib (VS-6063) were evaluated in patients with advanced solid tumours to establish the recommended phase II dose. Dose escalation followed a 3+3 design with a maximum of four patient cohorts. This arm is now complete. |
| Dose Expansion KRAS mutant NSCLC Cohort | EXPERIMENTAL | The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients with KRAS mutant NSCLC (20 patients). This arm is now complete. |
| Dose Expansion biopsy cohort | EXPERIMENTAL | The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients advanced RAS mutant solid tumours with biopsiable disease (6 patients). This arm is now complete. |
| Dose Expansion LGSOC cohort | EXPERIMENTAL | The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients with LGSOC (20 patients). |
| Dose Expansion CRC cohort | EXPERIMENTAL | The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients with CRC (10 patients). This arm is now complete. |
| Dose Expansion KRAS G12V mutant NSCLC cohort | EXPERIMENTAL | The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients with KRAS G12V mutant NSCLC (10 patients). |
| Dose Expansion RAS/RAF mutant endometrioid cancer cohort | EXPERIMENTAL | The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients with RAS/RAF mutant endometrioid subtype of gynaecological cancers (ovarian, endometrial, endometriosis-related) (10 patients). |
| Dose Expansion pancreatic cancer | EXPERIMENTAL | The dose expansion phase will evaluate the recommended phase II dose of the combination of VS-6766 (RO5126766) and Defactinib (VS-6063), as decided in the dose escalation phase in patients with pancreatic cancer (10 patients). |
| Name | Type | Description |
|---|---|---|
| VS-6766 | DRUG | Taken Orally |
| Abemaciclib | DRUG | Taken Orally |
| Fulvestrant | DRUG | Administered by intramuscular injection |
| Defactinib | DRUG | Defactinib is formulated as a white to off-white oval tablet for oral administration and supplied in single unit dose strength of 200 mg in 120 cc (HDPE) bottles. In addition to Defactinib, formulation components include microcrystalline cellulose, lactose monohydrate, sodium starch glycolate, and magnesium stearate. Patients will receive Defactinib orally immediately after a meal twice daily (approximately every 12 hours) for 3 weeks followed by 1 week off in every 4 week cycle. The starting dose will be 200mg. This can be escalated to a maximum of 400mg (as per dose escalation rules in the protocol). |
Inclusion Criteria: * Participants must have histologically or cytologically confirmed hormone receptor positive (HR+), HER2 negative metastatic or locally recurrent unresectable invasive breast cancer. ER, PR and HER2 measurements should be performed according to institutional guidelines, in a CLI...
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VS-6766 is an investigational small molecule being studied in oncology. Clinical trials are evaluating it in non-small cell lung cancer (NSCLC), breast cancer, colorectal cancer, low grade serous ovarian cancer, endometrioid carcinoma, and pancreatic cancer. It is also being studied in healthy subjects to assess food effects. It is not yet approved by the FDA.
VS-6766 is being developed by Verastem, Inc., a biopharmaceutical company traded on NASDAQ under the ticker VSTM. The company is conducting clinical trials of VS-6766 across multiple cancer types, including NSCLC, breast cancer, and colorectal cancer.
VS-6766 is in Phase 1 clinical development. Multiple Phase 1 trials are ongoing or completed, including studies in NSCLC, breast cancer, colorectal cancer, and a food effect study in healthy volunteers. VS-6766 is investigational and has not received FDA approval.
VS-6766 is being studied in several Phase 1 trials. NCT03875820 evaluates defactinib and VS-6766 in NSCLC, low grade serous ovarian cancer, endometrioid carcinoma, and pancreatic cancer. NCT05187169 is a completed food effect study in healthy adults. NCT05200442 studies VS-6766 with cetuximab in colorectal cancer. NCT05608252 studies VS-6766 with abemaciclib and fulvestrant in breast cancer.
Yes, VS-6766 is also known as VS-6766/avutometinib. This alternative name may appear in scientific literature and clinical trial listings. Both names refer to the same investigational small molecule being developed by Verastem, Inc.
No, VS-6766 is not FDA approved. It is an investigational drug currently in Phase 1 clinical trials. Studies are evaluating its safety and efficacy in various cancers, but it has not completed the clinical development process required for regulatory approval.