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This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with defactinib versus Investigator’s choice of treatments (ICT) in subjects with recurrent LGSOC who have progressed on a prior platinum-based therapy.

This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy and in combination with defactinib in subjects with recurrent Low-Grade Serous Ovarian Cancer (LGSOC)

This study will assess the safety and efficacy of avutometinib and sotorasib with or without defactinib in patients with G12C Non-Small Cell Lung Cancer (NSCLC) in patients who have been exposed to prior G12C inhibitor and those who have not been exposed to prior G12C inhibitor.

This study will assess the safety and efficacy of avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel in patients with Pancreatic Ductal Adenocarcinoma (PDAC) who have been previously untreated.

This is a multi-centre, investigator-initiated, dose escalation, Phase I trial of the combination of the FAK inhibitor, Defactinib (VS-6063), and the dual RAF/MEK inhibitor, avutometinib (VS-6766) in patients with advanced solid tumours. VS-6766 (RO5126766) is the same compound as CH5126766.

The purpose of this research is to test the effectiveness and safety of the study drugs ((avutometinib (VS-6766) and defactinib)), and see what effects (good and bad) these drugs have on the patients with endometrioid cancer, mucinous ovarian cancer, high-grade serous ovarian cancer, or cervical cancer.

This study will test if avutometinib (VS-6766) in combination with Defactinib is an effective treatment for advanced or recurrent mesonephric gynecologic cancer.

Doctors leading this study hope to learn about the safety of combining the study drug avutometinib (VS-6766) with another drug called cetuximab in colorectal cancer. This study is for individuals who have advanced colorectal cancer and their cancer has progressed while getting previous treatment or individuals who cannot take/tolerate previous treatments. If you choose to participate, your time in this research will last up to 24 months.

This research is being done to evaluate the safety and effectiveness of a drug currently known as avutometinib (VS-6766) in combination with the drugs abemaciclib and fulvestrant in HR+/HER2-negative breast cancer. The names of the study drugs involved in this study are: VS-6766 Abemaciclib Fulvestrant

In Part I of the study avutometinib (VS-6766) will be given twice weekly or three times per week in treatment cycles of 4 weeks to investigate a safe and tolerable dose of the drug. Once the optimal dosing schedule is defined, the following patients with BRAF, KRAS and/or NRAS mutations will be enrolled: 26 patients with solid tumours (Parts IIA & IIC) and 10 patients with Multiple Myeloma (Part IIB). Up to 44 patients with solid tumours containing BRAF, KRAS and/or NRAS mutations will take VS-6766 in combination with everolimus (Part IID). Of these, 20 patients will comprise the Part IID dose expansion and will all have KRAS-mutant lung cancer.