Coma S, Chowdhury S, Musteanu M, et al. Dual RAF/MEK inhibitor VS-6766 for treatment of solid tumors with diverse MAPK pathway alterations [abstract no. P121]. Mol Cancer Ther. 2021;20(12 Suppl)).

McCubrey JA, Steelman LS, Chappell WH, et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta. 2007;1773(8):1263–84.

CAS  PubMed  Google Scholar 

Zhu X, Bao Y, Guo Y, et al. Proline-rich protein tyrosine kinase 2 in inflammation and cancer. Cancers (Basel). 2018;10(5).

Banerjee S, Aghajanian C, Van Nieuwenhuysen E, et al. Efficacy and safety of avutometinib ± defactinib in recurrent low grade serous ovarian cancer: primary analysis of ENGOT-OV60/GOG-3052/RAMP 201 [abstract no. LB007/#1548 plus presentation]. Int J Gynecol Cancer. 2024;34(Suppl 3):A13.

Google Scholar 

Verastem Inc. AVMAPKITM FAKZYNJATM CO-PACK (avutometinib capsules; defactinib tablets), co-packaged for oral use: US prescribing information. 2025. https://www.verastem.com/pdf/avmapki-fakzynja-co-pack-full-prescribing-information.pdf. Accessed 7 Jul 2025.

U.S. Food & Drug Administration. FDA grants accelerated approval to the combination of avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer [media release]. 8 May 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-combination-avutometinib-and-defactinib-kras-mutated-recurrent-low.

Verastem Oncology. Verastem Oncology announces FDA acceptance and Priority Review of New Drug Application for avutometinib in combination with defactinib for the treatment of recurrent KRAS mutant low-grade serous ovarian cancer [media release]. 31 Dec 2024. http://www.verastem.com.

Verastem Oncology. Verastem Oncology receives Orphan Drug Designation from FDA for avutometinib alone or in combination with defactinib in recurrent low-grade serous ovarian cancer [media release]. 5 Mar 2024. http://www.verastem.com.

Verastem Oncology. Verastem Oncology receives Breakthrough Therapy Designation for VS-6766 with defactinib in recurrent low-grade serous ovarian cancer [media release]. 25 May 2021. http://www.verastem.com.

Verastem Inc. Verastem acquires clinical-stage FAK inhibitor from Pfizer [media release]. 11 Jul 2012. http://www.verastem.com.

Verastem Oncology. Verastem Oncology announces global licensing agreement with Chugai Pharmaceutical Co., Ltd. to develop and commercialize RAF/MEK inhibitor CH5126766 [media release]. 9 Jan 2020. http://www.verastem.com.

Yoshimura A, Horinaka M, Yaoi T, et al. Epithelial-mesenchymal transition status is a remarkable biomarker for the combination treatment with avutometinib and defactinib in KRAS-mutated non-small cell lung cancer. Br J Cancer. 2024;131(2):361–71.

CAS  PubMed  PubMed Central  Google Scholar 

Honda K, Yamamoto N, Nokihara H, et al. Phase I and pharmacokinetic/pharmacodynamic study of RO5126766, a first-in-class dual Raf/MEK inhibitor, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013;72(3):577–84.

CAS  PubMed  Google Scholar 

Martinez-Garcia M, Banerji U, Albanell J, et al. First-in-human, phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of RO5126766, a first-in-class dual MEK/RAF inhibitor in patients with solid tumors. Clin Cancer Res. 2012;18(17):4806–19.

CAS  PubMed  Google Scholar 

Jones SF, Siu LL, Bendell JC, et al. A phase I study of VS-6063, a second-generation focal adhesion kinase inhibitor, in patients with advanced solid tumors. Invest New Drugs. 2015;33(5):1100–7.

CAS  PubMed  Google Scholar 

Shimizu T, Fukuoka K, Takeda M, et al. A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016;77(5):997–1003.

CAS  PubMed  PubMed Central  Google Scholar 

McNamara B, Greenman M, Demirkiran C, et al. Pre-clinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition for low-grade serous ovarian cancer [abstract no. 38]. Gynecol Oncol. 2024;190(Suppl 1):S36.

Google Scholar 

Banerjee S, Krebs MG, Greystoke A, et al. Defactinib with avutometinib in patients with solid tumors: the phase 1 FRAME trial. Nat Med. 2025. https://doi.org/10.1038/s41591-025-03763-y.

Article  PubMed  PubMed Central  Google Scholar 

Banerjee SN, Ring KL, Van Nieuwenhuysen E, et al. Initial efficacy and safety results from ENGOT-ov60/GOG-3052/RAMP 201: a phase 2 study of avutometinib (VS-6766) +/- defactinib in recurrent low-grade serous ovarian cancer (LGSOC) [abstract no. 5515 plus poster]. J Clin Oncol. 2023;41(16_Suppl).

Reuss JE, Gandhi SG, Spigel DR, et al. RAMP 202: a phase 2 study of avutometinib (VS-6766) ± defactinib, in patients with advanced KRAS G12V mutant non–small cell lung cancer (NSCLC) [abstract no. 9100 plus poster]. J Clin Oncol. 2023;41(16_Suppl).

Lim K-H, Spencer KR, Safyan RA, et al. Avutometinib/defactinib and gemcitabine/nab-paclitaxel combination in first-line metastatic pancreatic ductal adenocarcinoma: initial safety and efficacy of phase 1b/2 study (RAMP 205) [abstract no. 4140 plus poster]. In: J Clin Oncol. 2024.

Lim K-H, Safyan RA, Perez K, et al. Avutometinib/defactinib and gemcitabine/nab-paclitaxel combination in first-line metastatic pancreatic ductal adenocarcinoma: updated safety and efficacy of a phase 1b/2 study (RAMP 205) [abstract no. e16403]. J Clin Oncol. 2025;43(16_Suppl).

Grisham RN, Praiss A, Iasonos A, et al. Single arm phase II study of avutometinib and defactinib in advanced or recurrent mesonephric or mesonephric-like (MLA) gynecologic cancer: interim results [presentation]. In: Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer. 2025.

Grisham R, Monk BJ, Van Nieuwenhuysen E, et al. GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301: a phase 3, randomized trial evaluating avutometinib plus defactinib compared with investigator’s choice of treatment in patients with recurrent low grade serous ovarian cancer. Int J Gynecol Cancer. 2025. https://doi.org/10.1136/ijgc-2024-005919.

Article  PubMed  Google Scholar 

Moy RH, Wu LW, Cho H, et al. Phase 2 trial of defactinib in combination with avutometinib in patients with advanced diffuse-type gastric cancer [abstract no. TPS505]. J Clin Oncol. 2025;43(4_Suppl).