Phase I Trial of Defactinib and VS-6766.

Summary

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, VS-6766 (RO5126766) in patients with advanced solid tumours. VS-6766 (RO5126766) is the same compound as CH5126766. There are two parts to this study, the dose escalation phase and the dose expansion phase. In the dose escalation phase, cohorts of 3 to 6 patients will be enrolled to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). This will be followed by a dose expansion phase to further characterise the safety and tolerability and to assess the pharmacodynamic activity of the combination.

Timeline

Start

2017-12-12

Primary completion

2023-04-30

Completion

2026-10-31

Publications

• Banerjee S, Krebs MG, Greystoke A, Garces AI, Perez VS, Terbuch A, Shinde R, Caldwell R, Grochot R, Rouhifard M, Ruddle R, Gurel B, Swales K, Tunariu N, Prout T, Parmar M, Symeonides S, Rekowski J, Yap C, Sharp A, Paschalis A, Lopez J, Minchom A, de Bono JS, Banerji U. Defactinib with avutometinib in patients with solid tumors: the phase 1 FRAME trial. Nat Med. 2025 Sep;31(9):3074-3080. doi: 10.1038/s41591-025-03763-y. Epub 2025 Jun 27.
• Fard D, Giraudo E, Tamagnone L. Mind the (guidance) signals! Translational relevance of semaphorins, plexins, and neuropilins in pancreatic cancer. Trends Mol Med. 2023 Oct;29(10):817-829. doi: 10.1016/j.molmed.2023.07.009. Epub 2023 Aug 17.

Drugs

Indications